Cancer Research and Treatment

Special Article

Utilization, Reimbursement, and Barriers to Accessing Sequencing Tests for Cancer Care in the Asia-Pacific Region: KSMO Initiatives to Address Cancer Care Inequity: Omali Pitiyarachchi, Aaron C. Tan, Tawasapon Thambamroong, Rogelio Velasco Jr, Yuji Uehara, Daphne Lee, Hsiang-Fong Kao, Vivek Agarwala, Yueh Ni Lim, Dimas Priantono, Ardhi Rahman Ahani, Kyaw Zin Win, Young Saing Kim, Changhoon Yoo; Received August 20, 2025 Accepted December 18, 2025 Published online December 19, 2025; DOI: https://doi.org/10.4143/crt.2025.896 [Accepted]

Abstract PDF: Purpose
The Asia Pacific region is marked by healthcare diversity and economic disparity.
Materials and Methods
To understand the utilization and reimbursement practices of next-generation sequencing (NGS) and other sequencing methods relevant to oncology clinical practice in the region, a semi-structured survey was undertaken of respondents from 11 countries represented by the Korean Society of Medical Oncology (KSMO) 2024 Young Oncologist Forum alumni.
Results
While 79% of respondents reported access to NGS at their institution, full government reimbursement was uncommon and varied by test type and clinical setting. Japan and South Korea offered the most comprehensive public coverage, including for circulating tumor deoxyribonucleic acid (ctDNA)-based liquid biopsy. Lower- and upper-middle-income countries, such as the Philippines, Indonesia, and India, reported no government reimbursement, thus relying on user-pay methods or private insurance payments. One marked barrier to NGS reimbursement was the prohibitive cost of tests (100%), followed by a limited budget to fund testing (79%), and then by policy or regulatory restrictions (50%). On a similar note, insurance coverage (93%) and patient income (86%) were key concerns regarding access and equity to tests. Test reimbursement (or lack thereof) and cost were cited almost universally as the most elevated concerns by the respondents.
Conclusion
The findings demonstrated a wide disparity in access, funding and reimbursement of sequencing tests across the region. Addressing cost, improving reimbursement mechanisms, and building infrastructure capacity will be critical for the equitable integration of NGS into routine cancer care in the Asia-Pacific.

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Original Articles

Longitudinal Circulating Tumor DNA Profiling as a Biomarker for Response and Resistance in Platinum-Refractory Head and Neck Squamous Cell Carcinoma: Wonyoung Choi, Jong-Ho Lee, Junsun Ryu, Sung Weon Choi, Yuh-Seog Jung, Joo-Yong Park, Chang Hwan Ryu, Sung Yong Choi, Weon Seo Park, Sun-Young Kong, Tak Yun; Received October 5, 2025 Accepted November 3, 2025 Published online November 4, 2025; DOI: https://doi.org/10.4143/crt.2025.1089 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
Immune checkpoint inhibitors (ICIs) are the standard treatment for platinum-refractory head and neck squamous cell carcinoma (HNSCC). This study aimed to characterize genomic alterations, monitor dynamic changes in circulating tumor DNA (ctDNA) associated with treatment response, and identify novel alterations linked to resistance through serial ctDNA profiling.
Materials and Methods
Patients with platinum-refractory HNSCC receiving nivolumab were enrolled. ctDNA was analyzed using FoundationOne Liquid CDx at baseline, 6 weeks after treatment, and at disease progression.
Results
A total of 36 patients were enrolled, and 33 were evaluable for ctDNA. The most frequent baseline alterations were TP53 (75.8%), followed by TERT (27.3%), NOTCH1 (24.2%), CDKN2A (12.1%), and CCND1 (12.1%). Of 27 patients with measurable lesions, five achieved a partial response with a response rate of 18.5%. Dynamic ctDNA profiling revealed all responders had marked reductions in both the sum of variant allele frequencies (sumVAF) and the maximum variant allele frequencies (maxVAF) across detected mutations. A decrease in sumVAF or maxVAF correlated with longer treatment durations, and patients with a > 50% decrease in either sumVAF or maxVAF showed significantly longer progression-free survival. Additionally, serial profiling identified de novo mutations in 17 patients, detected during stable disease or progression.
Conclusion
Serial ctDNA analysis provides a noninvasive tool for monitoring treatment response and detecting emerging resistance in HNSCC treated with ICIs. A significant reduction in ctDNA at 6 weeks was associated with improved clinical outcomes and warrants validation in larger, prospective studies to define its role as a predictive biomarker in HNSCC.

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Tumor-Type–Specific Tumor Mutational Burden Cutoffs for Improved Immune Checkpoint Inhibitor Outcome Prediction: Large-Scale Analysis with Real-World Targeted Next-Generation Sequencing Data: Ha Ra Jun, Ji-Young Lee, Changseon Lee, Sung-Min Chun; Received August 12, 2025 Accepted September 18, 2025 Published online September 19, 2025; DOI: https://doi.org/10.4143/crt.2025.860 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader: Purpose
Tumor mutational burden (TMB) is a potential biomarker for predicting response to immune checkpoint inhibitors (ICIs). However, its clinical utility is limited by methodological inconsistencies. This study aimed to evaluate the predictive value of TMB for ICI outcomes using next-generation sequencing (NGS) data.
Materials and Methods
We retrospectively analyzed 9,459 patients with cancer who underwent tumor-only targeted NGS. TMB-high (TMB-H) cutoffs were defined using an interquartile range (IQR)–based method and validated by comparing the overall survival (OS) and progression-free survival (PFS) in ICI-treated cohorts against both The Cancer Genome Atlas whole-exome sequencing–derived TMB and the universal 10 mutations per megabase (mut/Mb) cutoff. We also examined programmed cell death-ligand 1 (PD-L1) expression and subclonality to address response heterogeneity.
Results
IQR-based TMB-H was significantly associated with longer PFS in the ICI-treated cohort (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.73 to 0.98; p=0.022), NGS before ICI subgroup (HR, 0.86; p=0.049), and pre-ICI subgroup (HR, 0.80; p=0.026). In contrast, the universal 10 mut/Mb cutoff showed no statistical significance. Subgroup analysis revealed significant PFS benefit in bladder (p=0.014), bowel (p=0.013), and uterine cancers (p=0.006). In lung cancer, patients with both TMB-H and very high PD-L1 expression (≥ 90%) had the longest PFS (HR, 0.64; 95% CI, 0.44 to 0.93; p=0.021). Among the TMB-H samples, high subclonality was associated with worse OS in non-hypermutated cases (p=0.032).
Conclusion
Real-world TMB cutoffs derived from distribution-based methods offer improved predictive value for ICI outcomes. Integration of the PD-L1 expression and subclonality status further refines the predictive utility of TMB, improving precision in ICI treatment.

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Long-term Prognostic Value and Analytical Parameters of the Next-Generation Sequencing–Based Multigene Assay in Hormone Receptor–Positive, HER2-Negative Breast Cancer: Hyunji Kim, Jiwon Koh, Hyunwoo Lee, Gyungyub Gong, Sujin Oh, Jiyoung Lee, Ho Eun Chang, Yunhee Choi, Eunhye Kang, Jai Min Ryu, Dong Seung Shin, Sae Byul Lee, Hee Jin Lee, Hong-Kyu Kim, Hee-Chul Shin, Wonshik Han, Han-Byoel Lee, Kyoung Un Park; Received July 7, 2025 Accepted August 29, 2025 Published online September 1, 2025; DOI: https://doi.org/10.4143/crt.2025.701 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
In hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative early breast cancer, gene expression testing facilitates treatment decisions. A next-generation sequencing (NGS)–based assay was developed to address test decentralization and underrepresentation of younger/premenopausal patients. We aimed to validate the long-term prognostic value of the NGS-based assay and analyze its quality control (QC) parameters.
Materials and Methods
We analyzed samples from 265 patients with breast cancer with at least 10 years of follow-up. We evaluated the long-term prognostic ability of the NGS-based assay according to the risk groups for distant recurrence, as determined by the Decision Index, and the performance of the QC parameters used for the experimental process.
Results
Among 265 participants, 60.4% were ≤ 50 years old, and 39 (14.7%) experienced distant recurrence within 10 years. In the Decision Index–stratified low- and high-risk groups (n=186, 70.2% and n=79, 29.8%), 10-year distant metastasis–free survival rates were 96.1% (95% confidence interval [CI], 92.1 to 98.1) and 79.3% (95% CI, 68.4 to 86.8), respectively. In patients aged ≤ 50 years, the high-risk group had a hazard ratio of 5.89 (95% CI, 2.84 to 12.20). Analyses including 106 samples that failed the stringent QC criteria showed inferior prognostic value, wherein DV200 and cDNA concentrations were the most crucial parameters.
Conclusion
We validated the prognostic ability of an NGS-based assay to stratify HR-positive/HER2-negative breast cancers and predict the risk of distant recurrence, and confirmed the requirement for stringent QC criteria to ensure its prognostic ability.

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Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non-Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data: Hayoung Seong, Soo Han Kim, Mi-Hyun Kim, Ahrong Kim, Ju Sun Song, Jung Seop Eom; Received January 28, 2025 Accepted August 19, 2025 Published online August 25, 2025; DOI: https://doi.org/10.4143/crt.2025.114 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Comprehensive genomic profiling of early-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations remains limited. This study aimed to investigate genomic profiles of early- and advanced-stage EGFR-mutant NSCLC and identify potential innate resistance mechanisms to EGFR-tyrosine kinase inhibitors (TKIs) using targeted next-generation sequencing (NGS).
Materials and Methods
This retrospective observational study analyzed genomic profiles of patients with early-stage (IA-IIIA) and advanced-stage (IIIB-IV) EGFR-mutant NSCLC from the Lung Cancer NGS registry. Targeted NGS was performed to assess concurrent genetic alterations (GAs), tumor mutational burden (TMB), and variant allele frequency (VAF) of EGFR mutations.
Results
Overall, 160 patients (100 early-stage and 60 advanced-stage) were analyzed. The proportion of patients with concurrent GAs was not significantly different between stages (82.0% vs. 91.7%, p=0.092). Median TMB was 3.8 mutations/Mb in both stages, with no significant difference (p=0.206). However, the median VAF of EGFR mutations was significantly lower in early-stage compared to that in advanced-stage (19.3% vs. 29.6%, p=0.002). While TMB remained unchanged with disease progression (p=0.192), VAF of EGFR mutations increased significantly (p < 0.001). Moreover, the frequencies of concurrent single nucleotide variants and copy number variants were significantly lower in early-stage NSCLC.
Conclusion
Genomic heterogeneity in EGFR-mutant NSCLC arises early in tumorigenesis. The comparable TMB and lower VAF of EGFR mutations in early-stage disease suggest that innate resistance to EGFR-TKIs may be driven by concurrent GAs, supporting the consideration of combination therapies even in early-stage EGFR-mutant NSCLC.

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Keratin 6A Overexpression in the Lymphovascular Invasion–Associated Tumor Subgroup Promotes Progression of Triple-Negative Breast Cancer: Wei Luo, Yiping Zou, Yantao Jiang, Xi Ma, Shuyue Guo, Yao Wang, Yuxiao Liu, Linyue Hai, Wenbin Jia, Wenbo Liu, Ran Meng, Xuchen Cao, Xianhui Ruan, Yue Yu; Received April 17, 2025 Accepted July 11, 2025 Published online July 14, 2025; DOI: https://doi.org/10.4143/crt.2025.423 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Lymphovascular invasion (LVI) is a strong predictor of poor prognosis in triple-negative breast cancer (TNBC), yet its molecular basis remains unclear. This study investigates epithelial regulators associated with LVI and their functional roles in TNBC progression.
Materials and Methods
We utilized single-cell sequencing data to further characterize epithelial cell populations in TNBC, identifying dominant epithelial clusters in LVI-positive TNBC tissues. The prognostic significance of dominant epithelial marker genes was explored through transcriptomic analysis and immunohistochemical staining of patient samples from our center. Additionally, the effects of the marker gene on TNBC cell invasion and metastasis were validated in vitro and in vivo.
Results
Single-cell data analysis revealed nine distinct epithelial cell clusters within TNBC tissues. Among these, cluster 4 was identified as the dominant epithelial subpopulation in LVI-positive TNBC, marked by the prognostic gene KRT6A. Multiple datasets confirmed KRT6A as a crucial prognostic marker in TNBC. Functional assays, including Cell Counting Kit-8, wound healing, transwell assays, and animal experiments, demonstrated that KRT6A knockdown significantly impaired the proliferation, invasion, and metastatic potential of TNBC cells. Mechanistically, KRT6A promoted epithelial-mesenchymal transition (EMT) and activated Wnt/β-catenin signaling by stabilizing β-catenin through glycogen synthase kinase-3β phosphorylation.
Conclusion
KRT6A promotes EMT and metastasis in TNBC via Wnt/β-catenin signaling, contributing to LVI and chemoresistance. It may serve as a prognostic biomarker and therapeutic target in TNBC.

Citations

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Targeting keratin 6 A overcomes gemcitabine resistance by restoring equilibrative nucleoside transporter 1 and TAM-mediated metabolic compensation in pancreatic cancer
Junfeng Zhang, Xianxing Wang, Silue Zeng, Bo Tang, Xinyi Yang, Shaowen Xie, Haihan Sun, Ru Wang, Renpei Xia, Jinghe Li, Huaizhi Wang, Zhitian Shi, Jianyou Gu, Dong Wei
Drug Resistance Updates.2026; 87: 101404. CrossRef
Signaling Networks Regulating Metastatic Progression in Triple-Negative Breast Cancer
Zuzanna Senkowska, Katarzyna Owczarek, Karolina Niewinna, Urszula Lewandowska
Cells.2026; 15(9): 809. CrossRef
Inhibition of IGF1R in Early MMTV-Wnt1 Mammary Tumors: A Transcriptomic Analysis
Joseph J. Bulatowicz, Alexander Lemenze, Elvan Dogan, Christopher A. Galifi, Krystopher Maingrette, Quan Shang, Teresa L. Wood
Cancers.2026; 18(11): 1749. CrossRef

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Lung and Thoracic cancer

The Role of Circulating Tumor Cell as a Promising Biomarker in the Evaluation of Pulmonary Nodules: A Prospective Study: Shijie Wang, Changdan Xu, Xiaohong Xu, Weipeng Shao, Guohui Wang, Xiongtao Yang, Liwei Gao, Feng Teng, Hongliang Sun, Yue Zhao, Hongxiang Feng, Guangying Zhu; Cancer Res Treat. 2026;58(1):128-140. Published online March 27, 2025; DOI: https://doi.org/10.4143/crt.2024.841

Abstract PDF Supplementary Material PubReader ePub

Purpose
Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis.
Materials and Methods
Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted.
Results
A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases.
Conclusion
CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

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Integrated CT Radiomics and Circulating Tumor Cell Analysis in Predicting Lung Adenocarcinoma Invasion: A Dual-Center Study with Implications for Personalized Treatment
Qingtao Zhao, Runzhe Wang, Qingxin Zhao, Dahu Ren, Lingxin Kong, Xiaopeng Zhang, Guochen Duan
OncoTargets and Therapy.2026; Volume 19: 1. CrossRef
Establishment of a multi-targeted magnetic combined enrichment system for circulating tumor cells in gastric cancer and analysis of their genomic profiles
Linfei Huang, Yuelu Ruan, Lei Zhu, Jing Xu
Journal of Biomaterials Applications.2026;[Epub] CrossRef

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General

Epidermal Growth Factor Receptor Aberrations Identified by Next-Generation Sequencing in Patients with Metastatic Cancers: Minkyue Shin, Dae-Ho Choi, Jaeyun Jung, Deok Geun Kim, Minae An, Sung Hee Lim, Seung Tae Kim, Jung Yong Hong, Se Hoon Park, Joon Oh Park, Kyoung-Mee Kim, Jeeyun Lee; Cancer Res Treat. 2025;57(4):932-941. Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2024.564

Abstract PDF Supplementary Material PubReader ePub: Purpose
The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.
Materials and Methods
We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center. We analyzed the distribution of EGFR amplification, mutation, and fusion, as well as their correlations with microsatellite instability (MSI), tumor mutation burden (TMB), and other gene aberrations.
Results
A total of 3,286 patients were tested using NGS of a panel covering 523 cancer-related genes (TSO500, Illumina) as part of clinical practice between October 2019 and October 2022. Patients with lung cancer and gliomas were not included in the analysis. Of the 3,286 patients, 175 (5.3%) had EGFR amplification, 38 (1.2%) had EGFR mutations, and eight (0.2%) had EGFR fusion. All 175 patients with EGFR amplifications had microsatellite-stable tumors, but 102 had co-amplifications in other cancer-related genes, and 78 had mutations with clinical significance (tier I/II). Among the 38 patients with EGFR mutations, three (8%) showed MSI-high status, and 11 (29%) demonstrated high TMB (≥ 10 mutations/Mb). Among eight patients with EGFR fusion, three exhibited possible functionalities of the EGFR gene.
Conclusion
EGFR aberrations, mainly amplification, followed by mutation and fusion, were present in 6.4% of patients with metastatic solid tumors.

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Gastrointestinal cancer

Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers: Hyun Gu Lee, Yeseul Kim, Mi-Ju Kim, Yeon Wook Kim, Sun-Young Jun, Deokhoon Kim, In Ja Park, Seung-Mo Hong; Cancer Res Treat. 2026;58(1):264-274. Published online February 18, 2025; DOI: https://doi.org/10.4143/crt.2024.947

Abstract PDF Supplementary Material PubReader ePub: Purpose
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
Materials and Methods
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor.
Results
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
Conclusion
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

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Hematologic malignancy

Unraveling the Genetic Landscape of Langerhans Cell Histiocytosis in Korean Patients: Comprehensive Insights from Mutational Profiles and Clinical Correlations: Kyung-Nam Koh, Ha Ra Jun, Ji-Young Lee, Ji Young Kim, Su Hyun Yoon, Young Kwon Koh, Sung Han Kang, Hyery Kim, Ho Joon Im, Sung-Min Chun; Cancer Res Treat. 2025;57(3):873-882. Published online December 24, 2024; DOI: https://doi.org/10.4143/crt.2024.782

Abstract PDF PubReader ePub

Purpose
This study aimed to conduct a comprehensive genetic analysis of patients with Langerhans cell histiocytosis (LCH), focusing on the frequency of mitogen-activated protein kinase (MAPK) pathway mutations, detailed mutation profiles of MAPK pathway genes, and their correlation with clinical features and prognosis in Korean LCH patients.
Materials and Methods
We performed targeted next-generation sequencing, capable of capturing exons from 382 cancer-related genes, on genomic DNA extracted from formaldehyde-fixed and paraffin-embedded samples of 45 pathologically confirmed LCH patients.
Results
The majority of patients (91.1%) exhibited single-system disease, with bone being the most common location (84.4%). Initial treatments varied, and no patients died during a median follow-up of 6.8 years. Our genetic assays revealed that all patients had MAPK pathway alterations, including BRAF mutations in 51.2%, MAP2K1 mutations in 42.2%, RAF1 mutations in 4.4%, and a KRAS mutation in 2.2%. These mutations were mutually exclusive. Detailed mutation profiles indicated that among the BRAF mutations, there were 18 point mutations and five in-frame deletions, while most MAP2K1 mutations were in-frame deletions, with only one missense mutation. We detected previously unreported variations of point mutations in BRAF, MAP2K1, KRAS, and the first instance of a RAF1-KLC1 fusion in LCH. MAP2K1 mutations occurred more frequently in older patients, whereas BRAF V600 mutations were commonly associated with unifocal bone disease. Genetic mutations did not correlate with high-risk features or event-free survival.
Conclusion
This study identified mutually exclusive MAPK pathway mutations in every LCH patient through comprehensive genetic analysis, highlighting the importance of inclusive testing in understanding the disease’s genetics.

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Congenital Langerhans Cell Histiocytosis With Novel KLC1::RAF1 Gene Fusion Identified Through Routine Whole‐Genome Sequencing
Fiona E. Wright, Gemma Barnard, Shivani Bailey, C. Elizabeth Hook, Nicholas Coleman, Natasha Stembridge, Rowena Guermech, James Watkins, Jamie Trotman, Patrick Tarpey, Vasanta Nanduri, Matthew J. Murray
Pediatric Blood & Cancer.2025;[Epub] CrossRef

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Head and Neck cancer

Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy: Eun Joo Kang, Shinwon Hwang, Yun-Gyoo Lee, Jong-Kwon Choi, Seong Hoon Shin, Yoon Hee Choi, Keun-Wook Lee, Hyun Woo Lee, Min Kyoung Kim, Seung Taek Lim, Hwan Jung Yun, Sang-Gon Park, Sangwoo Kim, Sung-Bae Kim, Hye Ryun Kim; Cancer Res Treat. 2025;57(3):709-719. Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.836

Abstract PDF PubReader ePub

Purpose
Tumor suppressor p53 (TP53) mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials and Methods
We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: group 1, alpelisib; group 2, poziotinib; group 3, nintedanib; and group 4, abemaciclib. If there was no identifiable target, the patients were allocated to group 5 (durvalumab±tremelimumab).
Results
TP53 mutations were detected in 116/179 patients (64.8%), more frequently in human papillomavirus–negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion
TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

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Early-Onset Oral Tongue Squamous Cell Carcinoma in the Absence of Traditional Risk Factors: A Case Report with Whole-Exome Sequencing Analysis
Evgeniy Aleksiev, Darina Lyudmilova Kachakova-Yordanova, Vanyo Mitev, Martin Marinov Georgiev, Zornitsa Mihaylova
Reports.2026; 9(2): 130. CrossRef

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Breast cancer

Prognostic Performance of the Next-Generation Sequencing-Based Multigene Assay in Early Breast Cancer Patients Treated According to the 21-Gene Assay Results: Eunhye Kang, Jong-Ho Cheun, Jeeyeon Lee, Jiwon Koh, Hyunwoo Lee, Ji-Young Park, Hee Jin Lee, Byeongju Kang, Woong Ki Park, Jeongeun Son, Bumjoon Kim, Woosung Chung, Wonshik Han, Han-Byoel Lee, Sae Byul Lee, Jai Min Ryu; Cancer Res Treat. 2025;57(3):749-759. Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.1035

Abstract PDF Supplementary Material PubReader ePub

Purpose
Multigene assays guide treatment decisions in early-stage hormone receptor-positive breast cancer. OncoFREE, a next-generation sequencing assay using 179 genes, was developed for this purpose. This study aimed to evaluate the concordance between the Oncotype DX (ODX) recurrence score (RS) and the OncoFREE Decision Index (DI) and to compare their performance.
Materials and Methods
We retrospectively collected tumor blocks from patients who underwent ODX and treatment between 2012 and 2022 at four tertiary hospitals and performed OncoFREE on these samples. Distant metastasis-free survival (DMFS) was compared using RS and DI, with score cut-offs of 25 and 20, respectively.
Results
Among 838 patients, a strong correlation was observed between RS and DI (Pearson correlation coefficient 0.83). At a median follow-up of 54 months, patients with high DI had significantly worse DMFS compared to those with low-DI (log-rank p < 0.001; hazard ratio [HR], 5.73; 95% confidence interval [CI], 1.87 to 17.57; multivariable p=0.048; HR, 3.45; 95% CI, 1.01 to 11.76). In 513 patients aged ≤ 50 years, DMFS was significantly different as a function of DI (p=0.035; HR, 3.98; 95% CI, 1.00 to 15.89) but not RS (p=0.792). Among 376 patients aged ≤ 50 years who avoided chemotherapy based on low-RS, 64 with high DI had worse DMFS (p=0.015; HR, 5.91; 95% CI, 1.17 to 29.78).
Conclusion
OncoFREE showed strong concordance with ODX and effectively identified high-risk patients, particularly in younger individuals. It could be an affordable alternative to ODX for guiding treatment in hormone receptor-positive early breast cancer.

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Clinicopathologic characteristics and lymph node status in the NAUTILUS clinical trial:KBCSG-21
Jai Min Ryu, Han-Byoel Lee, Wonshik Han, Il-Yong Chung, Se Hyun Ahn, Seeyoun Lee, Seho Park, Joon Jeong, Woosung Lim, Jeong Eon Lee, Eunhye Kang, Ji Hyun Chang, Kyung Hwan Shin, Jung Min Chang, Woo Kyung Moon, Eun-Kyu Kim
European Journal of Surgical Oncology.2026; 52(4): 111458. CrossRef
Prospective Single-Arm Study of Endocrine Therapies With Ovarian Function Suppression in Premenopausal Node-Positive Early Breast Cancer Patients With Low Genomic Risk (INTERSTELLAR Trial, KBCSG-25)
Sung Gwe Ahn, Sung Hoon Sim, Taewoo Kang, Eun-Kyu Kim, Jeong Eon Lee, Hyeong-Gon Moon, Jee Hyun Ahn, Woosung Lim, Hyun Jo Youn, Hyun-Ah Kim, Chang Ik Yoon, Jisun Kim, Byeongju Kang, Min Ho Park, Su Hwan Kang, Lee Su Kim, Soong June Bae, Yoonwon Kook, Kwan
Journal of Breast Cancer.2026; 29(1): 81. CrossRef

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General

Target-Enhanced Whole-Genome Sequencing Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel: Sangmoon Lee, Jin Roh, Jun Sung Park, Islam Oguz Tuncay, Wonchul Lee, Jung-Ah Kim, Brian Baek-Lok Oh, Jong-Yeon Shin, Jeong Seok Lee, Young Seok Ju, Ryul Kim, Seongyeol Park, Jaemo Koo, Hansol Park, Joonoh Lim, Erin Connolly-Strong, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn, Hyun Woo Lee, Seokhwi Kim, Jang-Hee Kim, Minsuk Kwon; Cancer Res Treat. 2025;57(2):350-361. Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.114

Abstract PDF Supplementary Material PubReader ePub

Purpose
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS.
Materials and Methods
This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches.
Results
TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making.
Conclusion
TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Citations

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Whole-genome landscapes of 1,364 breast cancers
Ryul Kim, Jonghan Yu, Joonoh Lim, Brian Baek-Lok Oh, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung Joo Chae, Ji-Yeon Kim, Ga Eun Park, Bong Joo Kang, Pill Sun Paik, Soo Yeon Bae, Chang Ik Yoon, Young Joo Lee, Dooreh Kim, Kabsoo Shin, Ji Eun Lee, Jun Ka
Nature.2026; 649(8099): 1282. CrossRef
Pan-Cancer Targeted Sequencing Reveals Genomic Heterogeneity and Prognostic Subgroups in Urothelial Bladder Cancer
Dimitar Ugrinovski, Skender Saidi, Viktor Stankov, Martina Ambardjieva, Slavica Josifovska, Anne-Katrin Koehler, Joerg Gabert, Sasho Panov
Cancers.2026; 18(6): 1026. CrossRef

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Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Comprehensive analysis of FGFR2b and its correlation with essential biomarkers, intratumoral heterogeneity, and survival in advanced gastric cancer
Yoonjin Kwak, Tae-Yong Kim, Hye Seung Lee, Soo Kyung Nam, Hyeon Jeong Oh, Do-Youn Oh, Seock-Ah Im
British Journal of Cancer.2026; 134(10): 1429. CrossRef
Genomic and transcriptomic analyses of residual invasive triple-negative breast cancer after neoadjuvant chemotherapy in the prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab plus capecitabine compared to capecitabine; KCSG-B
S.-A. Im, K. Park, J. Koh, C. Park, K.H. Jung, J. Lee, H.K. Ahn, A. Lee, S.H. Sim, M.H. Kim, J.H. Kim, J.H. Kim, K.E. Lee, K.H. Park, J. Bae, M.H. Lee, S. Lim, H.J. Kim, D.-W. Lee, J.H. Jeong, K.S. Lee, J. Sohn, K.J. Suh, J.-Y. Kim, Y.J. Cha, J. Moon, C.-
ESMO Open.2025; 10(10): 105804. CrossRef

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Gastrointestinal cancer

Fecal Microbial Dysbiosis Is Associated with Colorectal Cancer Risk in a Korean Population: Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang; Cancer Res Treat. 2025;57(1):198-211. Published online July 26, 2024; DOI: https://doi.org/10.4143/crt.2024.382

Abstract PDF Supplementary Material PubReader ePub

Purpose
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods
In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion
Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

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Association analysis of the differences in intestinal flora and clinical tumor indicators among colorectal cancer patients
Lijun Ma, Wenjing Wang, Shihu Ma, Yanbai Wang, Hai Li, Ying Gao, Xiaoliang Xie
Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
Quantification of Naturally Occurring Prebiotics in Selected Foods
Arianna Natale, Federica Fiori, Federica Turati, Carlo La Vecchia, Maria Parpinel, Marta Rossi
Nutrients.2025; 17(4): 683. CrossRef

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Sarcoma

Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas: Yaolin Song, Guangqi Li, Zhenqi Zhang, Yinbo Liu, Huiqing Jia, Chao Zhang, Jigang Wang, Yanjiao Hu, Fengyun Hao, Xianglan Liu, Yunxia Xie, Ding Ma, Ganghua Li, Zaixian Tai, Xiaoming Xing; Cancer Res Treat. 2025;57(1):250-266. Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.343

Abstract PDF Supplementary Material PubReader ePub

Purpose
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

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An interpretable model based on weakly supervised learning for uterine smooth muscle tumor diagnosis: A multi-center study
Xiaoxi Wang, Xiaochen Shen, Moxuan Yang, Ling Yang, Ying He, Yanni Ren, Shuhao Wang, Dayi Wu, Yuanyuan Guo, Yiru Niu, Kaiyue Peng, Zhihui Wang, Jingpeng Wu, Jiacheng Li, Wei Wang, Feng Wang, Lijuan Cui, Wei Wang, Congrong Liu, Dingrong Zhong
Pathology - Research and Practice.2026; 278: 156337. CrossRef
Integrated mutational landscape analysis of endometrial stromal sarcoma
Tobias M. P. Hartwich, Seungji Choi, Ayoung Hwang, Stefania Bellone, Luca Palmieri, Hae Seo, Taekeun Kim, Juhyeon Hong, Camilla Krakstad, Jone Trovik, Ingunn M. Stefansson, Hans Kristian Haugland, Michelle Greenman, Victoria Ettorre, Sarah Ottum, Cem Demi
Proceedings of the National Academy of Sciences.2026;[Epub] CrossRef
Liquid Biopsy in Uterine Leiomyosarcoma: Current Biomarkers, Emerging Technologies, and Future Perspectives
Danru Zhang, Hongbo Wang
Current Oncology Reports.2026;[Epub] CrossRef
Subtype-Specific Prognosis, Recurrence Patterns, and Molecular Features in 148 Chinese Uterine Sarcomas: A Real-World Study
Ting Huang, Xinyu Xie, Xinqiao Du, Xiuling Sun, Guo Zhang, Jianliu Wang
Cancers.2026; 18(11): 1689. CrossRef
Mitochondrial Ribosomal Proteins and Cancer
Huiyi Wu, Xiaowei Zhu, Huilin Zhou, Min Sha, Jun Ye, Hong Yu
Medicina.2025; 61(1): 96. CrossRef
Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches
Alice Costa, Annalisa Astolfi, Livia Gozzellino, Margherita Nannini, Gianandrea Pasquinelli, Maria Abbondanza Pantaleo
Biomolecules.2025; 15(2): 265. CrossRef
Uncertainty-driven hybrid-view adaptive learning for fully automated uterine leiomyosarcoma diagnosis
Qi Li, Jingxian Wu, Xiyu Liu, Dengwang Li, Jie Xue
Medical Image Analysis.2025; 105: 103692. CrossRef
2.5D deep learning radiomics and clinical data for predicting occult lymph node metastasis in lung adenocarcinoma
Xiaoxin Huang, Xiaoxiao Huang, Kui Wang, Haosheng Bai, Xiuxian Lu, Guanqiao Jin
BMC Medical Imaging.2025;[Epub] CrossRef
A four-gene signature identified by integrated transcriptomic analysis for differential diagnosis and prognosis of uterine smooth muscle tumors
Huiyi Hu, Yuanqun Chen, Bo Hong, Jia Liu, Yuchen Jiang, Zhiying Yu, Zhi-Jie Xiao, Jing Li
Frontiers in Oncology.2025;[Epub] CrossRef

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General

Safe Utilization and Sharing of Genomic Data: Amendment to the Health and Medical Data Utilization Guidelines of South Korea: Hyojeong Park, Jongkeun Park, Hyun Goo Woo, Hongseok Yun, Minho Lee, Dongwan Hong; Cancer Res Treat. 2024;56(4):1027-1039. Published online June 7, 2024; DOI: https://doi.org/10.4143/crt.2024.146

Abstract PDF Supplementary Material PubReader ePub

Purpose
In 2024, medical researchers in the Republic of Korea were invited to amend the health and medical data utilization guidelines (Government Publications Registration Number: 11-1352000-0052828-14). This study aimed to show the overall impact of the guideline revision, with a focus on clinical genomic data.
Materials and Methods
This study amended the pseudonymization of genomic data defined in the previous version through a joint study led by the Ministry of Health and Welfare, the Korea Health Information Service, and the Korea Genome Organization. To develop the previous version, we held three conferences with four main medical research institutes and seven academic societies. We conducted two surveys targeting special genome experts in academia, industry, and institutes.
Results
We found that cases of pseudonymization in the application of genome data were rare and that there was ambiguity in the terminology used in the previous version of the guidelines. Most experts (>~90%) agreed that the ‘reserved’ condition should be eliminated to make genomic data available after pseudonymization. In this study, the scope of genomic data was defined as clinical next-generation sequencing data, including FASTQ, BAM/SAM, VCF, and medical records. Pseudonymization targets genomic sequences and metadata, embedding specific elements, such as germline mutations, short tandem repeats, single-nucleotide polymorphisms, and identifiable data (for example, ID or environmental values). Expression data generated from multi-omics can be used without pseudonymization.
Conclusion
This amendment will not only enhance the safe use of healthcare data but also promote advancements in disease prevention, diagnosis, and treatment.

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Conditional trust as a driver of public engagement in Korea’s national project of bio-big data
Jae Sun Kim, Seohyun Kim, Cheyeon Lee, Wonoh Jeong, Huiwon No, Sungsoo Lim, Yul Jung, Ilhak Lee, Kwangmo Yang
Frontiers in Genetics.2026;[Epub] CrossRef
The DtMin Protocol: Implementing Data Minimization Principles in Medical Information Sharing
Hyun-A Park
Electronics.2025; 14(8): 1501. CrossRef
질병관리청 기관생명윤리위원회 표준운영지침 개정 내용 소개
소연 박, 지민 임, 순영 손, 은교 곽
Public Health Weekly Report.2025; 19(5): 268. CrossRef

6,399 View
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Gastrointestinal cancer

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer: Jian Yang, Chengqing Yu, Haoran Li, Di Peng, Qiaoxia Zhou, Jun Yao, Juan Lv, Shuai Fang, Jiaochun Shi, Yijun Wei, Guoqiang Wang, Shangli Cai, Zhihong Zhang, Zixiang Zhang, Jian Zhou; Cancer Res Treat. 2024;56(4):1183-1196. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2023.1371

Abstract PDF Supplementary Material PubReader ePub

Purpose
Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC.
Materials and Methods
Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients.
Results
The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052).
Conclusion
Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

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Clinical performance of tumor-informed versus tumor-agnostic ctDNA assays for colorectal cancer recurrence: A systematic review and diagnostic accuracy meta-analysis
Daniel G. Camblor, Belén Martínez-Castedo, Jorge Martín-Arana, Francisco Gimeno-Valiente, Blanca García-Micó, Francisco Martínez-Picó, Víctor Seguí, Miguel García-Bartolomé, Diego González, Alejandro Guimera, Marisol Huerta, Susana Roselló, Valentina Gamb
Cancer Treatment Reviews.2026; 142: 103066. CrossRef
A new paradigm in postoperative colorectal cancer surveillance: integrating advanced imaging and multi-omics
Dongxue Yu, Jiandong Tai
Frontiers in Physiology.2026;[Epub] CrossRef
La gran oportunidad: La detección de la enfermedad mínima residual (EMR) en el cáncer colorrectal localizado mediante ADN tumoral circulante (ADNtc)
Eduardo Díaz-Rubio García
ANALES RANM.2026; 143(143(01)): 16. CrossRef
Circulating Tumor DNA as a Real-Time Biomarker for Minimal Residual Disease and Recurrence Prediction in Stage II Colorectal Cancer: A Systematic Review and Meta-Analysis
Silvia Negro, Alessandra Pulvirenti, Chiara Trento, Stefano Indraccolo, Stefania Ferrari, Marco Scarpa, Emanuele Damiano Luca Urso, Francesca Bergamo, Salvatore Pucciarelli, Simona Deidda, Angelo Restivo, Sara Lonardi, Gaya Spolverato
International Journal of Molecular Sciences.2025; 26(6): 2486. CrossRef
Cancer in a drop: Advances in liquid biopsy in 2024
Roberto Borea, Erick F. Saldanha, Shivahamy Maheswaran, Eleonora Nicolo, Surbhi Singhal, Letizia Pontolillo, Diego de Miguel Perez, Konstantinos Venetis, Angelo Dipasquale, Nadia Ghazali, Pasquale Pisapia, Ana Ortega Franco, Mohamed A. Gouda, Carolina Red
Critical Reviews in Oncology/Hematology.2025; 213: 104776. CrossRef
Prognostic significance of circulating tumor DNA in non-metastatic colorectal cancer
Ruiyang Li, Shuchao Wang, Jie Xu, Min Zhao, Heng Zhang, Yibo Yin, Xue Han, Baojun Liu, Wenjian Liu
Discover Oncology.2025;[Epub] CrossRef

5,416 View
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Genitourinary cancer

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy: Bokyung Ahn, Doeun Kim, Kye Jin Park, Ja-Min Park, Sun Young Yoon, Bumsik Hong, Yong Mee Cho, Deokhoon Kim; Cancer Res Treat. 2024;56(3):856-870. Published online December 18, 2023; DOI: https://doi.org/10.4143/crt.2023.1150

Abstract PDF Supplementary Material PubReader ePub

Purpose
In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.
Materials and Methods
Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.
Results
Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001).
Conclusion
According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

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Papillary renal neoplasm with reverse polarity shows benign behavior: Results from a 77-case clinicopathological and molecular study
Yong Il Lee, Ja-Min Park, Sun Young Yoon, Cheryn Song, Yong Mee Cho
Annals of Diagnostic Pathology.2026; 80: 152498. CrossRef
Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience
Jianping Zhao, Yuan Shen, Ming Guo, Surena F Matin, Donna E Hansel, Charles C Guo
American Journal of Clinical Pathology.2024;[Epub] CrossRef
Clinical Significance of Tumor Location for Ureteroscopic Tumor Grading in Upper Tract Urothelial Carcinoma
Satoshi Katayama, Benjamin Pradere, Nico C. Grossman, Aaron M. Potretzke, Stephen A. Boorjian, Alireza Ghoreifi, Siamak Daneshmand, Hooman Djaladat, John P. Sfakianos, Andrea Mari, Zine-Eddine Khene, David D’andrea, Nozomi Hayakawa, Kazutoshi Fujita, Axel
Journal of Endourology.2024; 38(11): 1156. CrossRef
Development and validation of a radiomics-based nomogram for predicting pathological grade of upper urinary tract urothelial carcinoma
Yanghuang Zheng, Hongjin Shi, Shi Fu, Haifeng Wang, Xin Li, Zhi Li, Bing Hai, Jinsong Zhang
BMC Cancer.2024;[Epub] CrossRef

5,726 View
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Special Article

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; Cancer Res Treat. 2024;56(3):721-742. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1043

Abstract PDF PubReader ePub

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Long-Term Response Without Immune-Related Adverse Events to Atezolizumab Treatment in TMB-High Thymoma: A Case Report from the KOSMOS-II Study
In Hee Lee, Moonsik Kim, An Na Seo, Soo Jung Lee, Jee Hyun Kim
Journal of Clinical Medicine.2026; 15(3): 958. CrossRef
Real-World Genomic Landscape of Korean Gastric Cancer: Integrating Biomarker Associations and Clinical Outcomes in Metastatic Gastric Cancer
Seong-Keun Yoo, Soomin Ahn, Jinha Hwang, Jongwu Kim, Yunjin Go, Minsuk Kwon, Sung Hee Lim, Seung Tae Kim, Kyoung-Mee Kim, Jeeyun Lee
JCO Precision Oncology.2026;[Epub] CrossRef
Real-World Data: Implementation and Outcomes of Next-Generation Sequencing in the MENA Region
Rami Mahfouz, Reine Abou Zeidane, Tasnim Diab, Ali Tarhini, Eman Sbaity, Houry Kazarian, Yomna El Zibaoui, Nour Sabiha Naji, Mounir Barake, Hazem I. Assi
Diagnostics.2025; 15(10): 1183. CrossRef
Exploring PIXE Applications in Oncology: A Comprehensive Review
G. J. Naga Raju
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Original Articles

Lung and Thoracic cancer

Tissue and Plasma-Based Highly Sensitive Blocker Displacement Amplicon Nanopore Sequencing for EGFR Mutations in Lung Cancer: Patinya Akkhasutthikun, Pornchai Kaewsapsak, Pattaraporn Nimsamer, Pavit Klomkliew, Suthida Visedthorn, Pragwalai Chanchaem, Chinachote Teerapakpinyo, Sunchai Payungporn, Sutima Luangdilok; Cancer Res Treat. 2024;56(2):455-463. Published online November 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1108

Abstract PDF Supplementary Material PubReader ePub

Purpose
The epidermal growth factor receptor (EGFR) mutation is a widely prevalent oncogene driver in non–small cell lung cancer (NSCLC) in East Asia. The detection of EGFR mutations is a standard biomarker test performed routinely in patients with NSCLC for the selection of targeted therapy. Here, our objective was to develop a portable new technique for detecting EGFR (19Del, T790M, and L858R) mutations based on Nanopore sequencing.
Materials and Methods
The assay employed a blocker displacement amplification (BDA)–based polymerase chain reaction (PCR) technique combined with Nanopore sequencing to detect EGFR mutations. Mutant and wild-type EGFR clones were generated from DNA from H1650 (19Del heterozygous) and H1975 (T790M and L858R heterozygous) lung cancer cell lines. Then, they were mixed to assess the performance of this technique for detecting low variant allele frequencies (VAFs). Subsequently, formalin-fixed, paraffin-embedded (FFPE) tissue and cell-free DNA (cfDNA) from patients with NSCLC were used for clinical validation.
Results
The assay can detect low VAF at 0.5% mutant mixed in wild-type EGFR. Using FFPE DNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and Cobas real-time PCR were 98.46%, 100%, and 100%, respectively. For cfDNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and droplet digital PCR were 94.74%, 100%, and 100%, respectively.
Conclusion
The BDA amplicon Nanopore sequencing is a highly accurate and sensitive method for the detection of EGFR mutations in clinical specimens.

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Long-read sequencing for cancer liquid biopsy: advancing precision oncology
Grace Guzman, Analiz Rodriguez
Frontiers in Oncology.2026;[Epub] CrossRef
Decoding EGFR A289 Mutation in Glioblastoma: A Predictive Biomarker Framework and Targeted Therapeutic Insights
Xiaoxue Zhu, Haitao Fu, Xuejing Li, Hang Zhou, Zekai Li, Luyang Xie, Guilin Li
Journal of Molecular Neuroscience.2025;[Epub] CrossRef
Bullous Congenital Ichthyosiform Erythroderma with Tinea Capitis in Half-Siblings: Rare Phenomenon in Ichthyosis with Co-Existing Trichophyton rubrum Infection and Blocker Displacement Amplification for Mosaic Mutation Detection
Jipeng Liu, Yujuan Fu, Qihao Zhang, Qi Chen, Yuxiang Yang, Yi Xue, Yunqing Ren
Biomedicines.2025; 13(8): 2015. CrossRef
Cancer liquid biopsies by Oxford Nanopore Technologies sequencing of cell-free DNA: from basic research to clinical applications
Hua-Qi Si, Peng Wang, Fei Long, Wei Zhong, Yuan-Dong Meng, Yuan Rong, Xiang-Yu Meng, Fu-Bing Wang
Molecular Cancer.2024;[Epub] CrossRef

7,010 View
269 Download
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Genomic Landscape of Pulmonary Sarcomatoid Carcinoma: Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung; Cancer Res Treat. 2024;56(2):442-454. Published online November 14, 2023; DOI: https://doi.org/10.4143/crt.2023.764

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

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A Phase II Study of Durvalumab, Doxorubicin, and Ifosfamide in Recurrent and/or Metastatic Pulmonary Sarcomatoid Carcinoma (KCSG LU-19-24)
Miso Kim, Jeonghwan Youk, Tae Min Kim, Gyeong-Won Lee, Dong-Wan Kim, Bhumsuk Keam
Clinical Lung Cancer.2026; 27(3): 58. CrossRef
Genomic characterization of pulmonary sarcomatoid adenocarcinoma: a paired whole-exome sequencing study of carcinomatous and sarcomatous components
Jing Lin, Yuzhong Yang, Mengqing Liu, Fan Yang, Shaofeng Jiang, Longkuan Xu, Xiang Zheng, Hui Wei, Xuyan Wen, Guining Xu, Ruolan Weng, Jinhua Zheng, Shengjun Xiao
Frontiers in Oncology.2026;[Epub] CrossRef
Pulmonary pleomorphic carcinoma associated with cystic airspace and recurrent spontaneous pneumothorax: A case report
Qiangsheng Li, Jing Zhang, Youjie Gong, Xudong Wan, Song Zhang, Zhongwang Li, Jun Liu
Oncology Letters.2025; 30(1): 1. CrossRef
Combination of epirubicin and cyclophosphamide for the treatment of advanced pulmonary sarcomatoid carcinoma: A case report and literature review
Ruoyu Deng, Jialing Lv, Fang Wang, Yanqiong Chen, Junfeng Wang, Lin Wang, Lixia Mu, Zhijun Zhang, Wen Zhang, Chao Zhang
Journal of Cancer Research and Therapeutics.2025; 21(2): 512. CrossRef
Challenges in the Recognition and Management of Metastatic Sarcomatoid Carcinoma Masquerading As Post-traumatic Hematoma
Abigayle Wyer, Mena Louis, Richard Adams, Raven Richardson, Ezra Ellis, Brian Gibson
Cureus.2025;[Epub] CrossRef
Distinct Clinicogenomic Features and Immunotherapy Associations in Pulmonary Sarcomatoid Carcinoma: A Multicenter Retrospective Study
Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J. Cooper, Joao V. Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Valentina Santo, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L. Gibbons, Ara A. Vaporc
Journal of Thoracic Oncology.2025; 20(12): 1763. CrossRef
Exceptional Response to Immunotherapy-based Treatment in Compound EGFR-Mutated Oligometastatic Pulmonary Sarcomatoid Carcinoma: A Case Report
Ayushi Gianchandani, Darshana Desai, Janani Sambath, Darshana Patil, Prashant Kumar, Shambhavi Singh, Chetan Madre, Ruturaj Deshpande, Anjali Parab, Niyati Shah, Darshit Shah, Pritam Kataria, Shrikanth Atluri, Marzi Mehta, Aditya Shreenivas, Rajan Datar,
Journal of Immunotherapy and Precision Oncology.2025; 8(3): 206. CrossRef
Immune Checkpoint Inhibitor Monotherapy for Patients With Pulmonary Sarcomatoid Carcinoma—The Optimal Therapeutic Strategy for This Rare Lung Cancer Subtype?
Jennifer M. Boland, Ying-Chun Lo, Aaron S. Mansfield
Journal of Thoracic Oncology.2025; 20(12): 1735. CrossRef
PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Ka
American Journal of Surgical Pathology.2024; 48(10): 1233. CrossRef

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Genitourinary cancer

Clear Cell Adenocarcinoma of Urethra: Clinical and Pathologic Implications and Characterization of Molecular Aberrations: Boram Song, Seok Hyun Lee, Jeong Hwan Park, Kyung Chul Moon; Cancer Res Treat. 2024;56(1):280-293. Published online September 11, 2023; DOI: https://doi.org/10.4143/crt.2023.577

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods
We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results
All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion
Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.

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Molecular characterization of clear cell adenocarcinoma of the urinary bladder
Shilpy Jha, Anandi Lobo, Ankur R Sangoi, Shivani R Kandukuri, Sourav K Mishra, Samriti Arora, Aditi Aggarwal, Shivani Sharma, Ekta Jain, Mahmut Akgul, Andres M Acosta, Niharika Pattnaik, Seema Kaushal, Manas Baisakh, Sudhasmita Routa, Nada Shaker, Jasrema
Histopathology.2026; 88(6): 1167. CrossRef
Clear Cell Adenocarcinoma of the Urinary Tract Arising in a Young Man With the Congenital Malformation Disorder Opitz Syndrome: A Case Report
Jessica F. Williams, Juan F. Santoscoy Gutierrez, José I. Nolazco, Graeme S. Steele, Kristine S. Burk, Michelle S. Hirsch, Natalie M. Rizzo
International Journal of Surgical Pathology.2026; 34(4): 1074. CrossRef
Histologic mimics of urothelial carcinoma
Douglas Jian-Xian Wu, Emily Chan
Seminars in Diagnostic Pathology.2026; 43(2): 150993. CrossRef
Clinical and Molecular Characterization of Clear Cell Adenocarcinoma of the Urinary Tract
Manju Aron, Darshan S. Chandrashekar, Eman Adulfatah, Lakshmi P. Kunju, Bassel Zein-Sabatto, João Lobo, Sofia Canete-Portillo, Roni M. Cox, Christopher G. Przybycin, Khaleel Al-Obaidy, Muhammad T. Idrees, Sara M. Falzarano, Angela J. Wu, Shuko Harada, Geo
American Journal of Surgical Pathology.2026; 50(6): 589. CrossRef
Primary urethral clear cell carcinoma: a rare case report
Jiaxiang Yi, Weigang Ren, Weijie Song, Yixing Duan
Frontiers in Oncology.2026;[Epub] CrossRef
Urethral clear cell adenocarcinoma in an adult female: A rare case report
Yacob Sheiferawe Seman, Michael Teklehaimanot Abera, Fadil Nuredin Abrar, Tesfaye Kebede Legesse, Mesfin Asefa Tola, Tsiyon Nigusie Alemu
Urology Case Reports.2025; 58: 102882. CrossRef
Two rare cases of primary clear cell adenocarcinoma of the urethra: clinical experience, case report and literature review
Bohao Jiang, Jiyuan Hu, Benqiao Wang, Xujia Liu, Ling Tong, Yitong Xu, Hao Zhang
Frontiers in Oncology.2025;[Epub] CrossRef
Comprehensive Molecular, Pathological, and Clinical Characterization of Clear Cell Adenocarcinoma of the Urinary Tract
Rayan Rammal, Florestan J. Koll, Ziyu Chen, Jacob E. Tallman, Syed Muneeb Alam, Jordan E. Eichholz, Walid Chatila, Tejiri Agbamu, Andrew T. Lenis, Merve Basar, Cansu Yol, Jie-Fu Chen, Judy Sarungbam, Ying-Bei Chen, Anuradha Gopalan, Samson W. Fine, Satish
Modern Pathology.2025; 38(10): 100821. CrossRef
Association between CACNA1D polymorphisms and hypospadias in a southern Chinese population
Ye He, Binyao Li, Xinying Zhao, Lingling Pan, Yanqing Liu, Chaoting Lan, Fuming Deng, Wen Fu, Yan Zhang, Xiaoyu Zuo
Journal of Pediatric Urology.2024; 20(3): 438.e1. CrossRef
The L‐type calcium channel CaV1.3: A potential target for cancer therapy
Xuerun Liu, Boqiang Shen, Jingyi Zhou, Juan Hao, Jianliu Wang
Journal of Cellular and Molecular Medicine.2024;[Epub] CrossRef

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General

Trends and Clinical Characteristics of Next-Generation Sequencing–Based Genetic Panel Tests: An Analysis of Korean Nationwide Claims Data: Mi Jang, Hae Yong Pak, Ja Yoon Heo, Hyunsun Lim, Yoon-La Choi, Hyo Sup Shim, Eun Kyung Kim; Cancer Res Treat. 2024;56(1):27-36. Published online September 7, 2023; DOI: https://doi.org/10.4143/crt.2023.844

Abstract PDF Supplementary Material PubReader ePub

Purpose
In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea.
Materials and Methods
This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs.
Results
Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020.
Conclusion
This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.

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Report of the Korean Association for External Quality Assessment of Next-Generation Sequencing Analysis for Somatic Variants in Hematologic Malignancies (2021–2025)
Dongju Won, Yu Jin Park, JoungEun Lee, Mijung Kwon, Saeam Shin, Seung-Tae Lee, Jong Rak Choi
Journal of Laboratory Medicine and Quality Assurance.2026; 48(1): 10. CrossRef
Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim,
Cancer Research and Treatment.2025; 57(2): 443. CrossRef
Evaluation of false positive and false negative errors in targeted next generation sequencing
Youngbeen Moon, Young-Ho Kim, Jong-Kwang Kim, Chung Hwan Hong, Eun-Kyung Kang, Hye Won Choi, Dong‑eun Lee, Tae-Min Kim, Seong Gu Heo, Namshik Han, Kyeong-Man Hong
Genome Biology.2025;[Epub] CrossRef

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3 Crossref

Breast cancer

Next-Generation Sequencing in Breast Cancer Patients: Real-World Data for Precision Medicine: Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho; Cancer Res Treat. 2024;56(1):149-161. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.800

Abstract PDF Supplementary Material PubReader ePub

Purpose
Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer.
Materials and Methods
We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500.
Results
The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation.
Conclusion
NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

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Application of PI3K inhibitors in breast cancer treatment: a clinical trial landscape analysis based on clinical trial databases and registries
Junjie Cao, Yanru Chen, Jiani Song, Shuang Li, Yalin Tang, Xinru Zhang, Lichuan Zhang, Lin Ma
Frontiers in Oncology.2026;[Epub] CrossRef
Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim,
Cancer Research and Treatment.2025; 57(2): 443. CrossRef
Comprehensive genomic profiling of Taiwanese triple-negative breast cancer with a large targeted sequencing panel
Chi-Cheng Huang, Yi-Chen Yeh, Han-Fang Cheng, Bo-Fang Chen, Chun-Yu Liu, Yi-Fang Tsai, Hsiang-Ling Ho, Ling-Ming Tseng
Journal of the Chinese Medical Association.2025; 88(8): 641. CrossRef
Perceived Barriers to NGS-Based Molecular Profiling Among US Metastatic Breast Cancer Patients
Nicholas Cadirov, Moumita Chaki, Olivia Foroughi, Omar Perez, Stella Redpath, Gary Gustavsen
Diagnostics.2025; 15(20): 2626. CrossRef
Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer
Elena Guerini-Rocco, Konstantinos Venetis, Giulia Cursano, Eltjona Mane, Chiara Frascarelli, Francesco Pepe, Mariachiara Negrelli, Edoardo Olmeda, Davide Vacirca, Alberto Ranghiero, Dario Trapani, Carmen Criscitiello, Giuseppe Curigliano, Christian Rolfo,
Critical Reviews in Oncology/Hematology.2024; 201: 104427. CrossRef
An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer
Yi Bi, Xiao Lv, Ke Wang, Jinyu Wu, Xiang Shi, Xiaodong Zheng, Xiaogang Lin
Frontiers in Bioengineering and Biotechnology.2024;[Epub] CrossRef
NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
Romanian Journal of Morphology and Embryology.2024; 65(2): 195. CrossRef

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Gastrointestinal cancer

Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis: Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim; Cancer Res Treat. 2024;56(1):219-237. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.340

Abstract PDF Supplementary Material PubReader ePub

Purpose
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

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Multi-gene DNA methylation profiles of tumor suppressor genes for prognostic prediction in gastric cancer
Soo Kyung Nam, Juhyeong Park, Yoonjin Kwak, Chinbayar Batochir, Eun-Bi Kim, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
BMC Cancer.2026;[Epub] CrossRef
Precision treatment of gastrointestinal tumours and liver disease interaction mechanisms based on multi-omics data and microbiome hubs
Bangxing Lin, Shizheng Tong, Chaokai Ba, Xiang Wang
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Ahmad Dawalibi, Mohamad Bakir, Khalid S. Mohammad
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TSPAN7 inhibits pancreatic cancer progression by suppressing DNA double-strand break repair and enhances sensitivity to immunochemotherapy
Hai Lin, Jiancong Zhou, Yaning Li, Lisi Luo, Yan Zeng, Xinyue Liang, Jiaping Yu, Chengying Ye, Pengfei Yang, Yujing Lin, Yufang Li, Linjuan Zeng
Biochemical Pharmacology.2025; 242: 117199. CrossRef
UBC9 overexpression promotes proliferation and metastasis in gastric cancer via ATF2
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World Journal of Surgical Oncology.2025;[Epub] CrossRef
Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis
Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu
OncoTargets and Therapy.2025; Volume 18: 873. CrossRef
Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall
Sara Polo-Alonso, Álvaro Hernáez, Irene Dégano, Ruth Martí-Lluch, Mel·lina Pinsach-Abuin, Roberto Elosua, Isaac Subirana, Marta Puigmulé, Alexandra Pérez, Raquel Cruz, Silvia Diz-de Almeida, Eulàlia Puigdecanet, Elisabet Selga, Xavier Nogues, Joan Masclan
International Journal of Molecular Sciences.2025; 26(18): 9252. CrossRef
Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness
Liudmila V. Spirina, Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Maxim Yu. Volkov, Sergey V. Vtorushin, Irina V. Kovaleva, Tatyana S. Klyushina, Igor O. Munkuev
Current Issues in Molecular Biology.2024; 46(2): 1281. CrossRef
SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway
Fan Li, Xiaohong Zhang, Li Feng, Xingxing Zhang
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Xi Cao, Yongchao Luo, Songjie Shen, Xinyu Ren
Oncology Letters.2024;[Epub] CrossRef

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ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer: Sung Hwan Lee, Jaekyung Cheon, Seoyoung Lee, Beodeul Kang, Chan Kim, Hyo Sup Shim, Young Nyun Park, Sanghoon Jung, Sung Hoon Choi, Hye Jin Choi, Choong-kun Lee, Hong Jae Chon; Cancer Res Treat. 2023;55(4):1291-1302. Published online May 3, 2023; DOI: https://doi.org/10.4143/crt.2022.1450

Abstract PDF Supplementary Material PubReader ePub

Purpose
There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC.
Materials and Methods
Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines.
Results
193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells.
Conclusion
Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

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Journal of Hepatology.2025; 82(4): 649. CrossRef
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A. I. Marzaganova, I. R. Martirosyan, A. S. Korchemkina, E. G. Avanesyan, D. A. Korkmazova, O. B. Grakhnova, V. V. Akimina, A. P. Dzhamalutdinova, D. A. Bolloev, A. M. Dugulbgova, Z. G. Bakhmudova, A. T. Salikhova, P. A. Dzigora
Obstetrics, Gynecology and Reproduction.2025; 19(2): 282. CrossRef
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Ozlem Yedier-Bayram, Ahmet Cingöz, Ebru Yilmaz, Ali Cenk Aksu, Beril Esin, Nareg Degirmenci, Ayse Derya Cavga, Beyza Dedeoğlu, Buse Cevatemre, Hamzah Syed, Martin Philpott, Adam P. Cribbs, Udo Oppermann, Nathan A. Lack, Ceyda Acilan, Tamer T. Onder, Tugba
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Hongsik Kim, Chiyoon Oum, Soo Ick Cho, Wonkyung Jung, Hong Jae Chon, Myung Ah Lee, Hyeon-Su Im, Min Hwan Kim, Taekjin Nam, Chan-Young Ock, Hye Jin Choi, Choong-kun Lee
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Giulia Tesini, Halima Ibrahim, Lorenza Rimassa, Chiara Braconi
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Jaida E. Morgan, Nishah Jaferi, Zainab Shonibare, Gloria S. Huang
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Koji Kameyama, Kosuke Mizutani, Tetsuya Yamada, Seiji Sugiyama, Shingo Kamei, Shigeaki Yokoi, Kengo Matsunaga, Koseki Hirade, Yasutaka Kato, Hiroshi Nishihara, Satoshi Ishihara, Takashi Deguchi
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Wei Zhou, Hao Chi, Xiaohu Zhao, Guangrong Tao, Jianhe Gan
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Jiumei Zhao, Jing Zhu, Yu Tang, Kepu Zheng, Ziwei Li
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15 Crossref

Gynecologic cancer

Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma: Nan Kang, Yinli Zhang, Shichao Guo, Ran Chen, Fangzhou Kong, Shuchun Wang, Mingming Yuan, Rongrong Chen, Danhua Shen, Jianliu Wang; Cancer Res Treat. 2023;55(3):978-991. Published online February 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1647

Abstract PDF PubReader ePub

Purpose
The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients.
Materials and Methods
A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored.
Results
TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion.
Conclusion
This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

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Beyond histology: Genomic profiling as a therapeutic compass in SMARCA4-deficient uterine sarcoma
Hardik Mahendrakumar Patel, Amrit Kaur Kaler, Sandeep Goyle, Amit Negi, Manali Ajagekar, Dushant Lakade, Riya Manoharan, Krisna Jariwala, Bijal Kulkarni, Anshumala Shukla, Yogesh Kulkarni
Journal of Diagnostic and Academic Pathology.2026; 3(1): 44. CrossRef
Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin Song, Guangqi Li, Zhenqi Zhang, Yinbo Liu, Huiqing Jia, Chao Zhang, Jigang Wang, Yanjiao Hu, Fengyun Hao, Xianglan Liu, Yunxia Xie, Ding Ma, Ganghua Li, Zaixian Tai, Xiaoming Xing
Cancer Research and Treatment.2025; 57(1): 250. CrossRef
Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches
Alice Costa, Annalisa Astolfi, Livia Gozzellino, Margherita Nannini, Gianandrea Pasquinelli, Maria Abbondanza Pantaleo
Biomolecules.2025; 15(2): 265. CrossRef
Risk factors, survival analysis, and nomograms for high-grade endometrial stromal sarcoma patients with distant metastasis: a population-based study (2010–2019)
Cheng Wang, Dongni Liang, Wei Kuang, Huanxin Sun, Yuling Kou, Wei Wang, Jing Zeng
Frontiers in Oncology.2025;[Epub] CrossRef
Endometrial Stromal Sarcoma: An Update
Giulio Ricotta, Silvio Andrea Russo, Anna Fagotti, Alejandra Martinez, Elodie Gauroy, Mathilde Del, Valentin Thibaud, Bataillon Guillaume, Gwenaël Ferron
Cancers.2025; 17(11): 1893. CrossRef
Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of Endometrial Stromal Sarcomas, Uterine Tumors Resembling Ovarian Sex Cord Tumors, and Undifferentiated Uterine Sarcomas With Prognostic Insights
Jan Hojný, Jiří Dvořák, Romana Vránková, Michaela Kendall Bártů, Nikola Hájková, Eva Krkavcová, Miroslava Flídrová, Ivana Stružinská, Kristýna Němejcová, Jiří Bouda, Květoslava Michalová, David Cibula, Renata Poncová, Janusz Rys, Mariusz Ksiazek, Marcin J
Laboratory Investigation.2025; 105(9): 104198. CrossRef
Immunotherapy for high-grade endometrial stromal sarcoma: a narrative review bridging molecular insights to clinical translation
Liubiqi Zhao, Yunyi Su1, Xiaoling Li, Fang Wang, Li He, Limei Fan, Lushuang Zhang
Frontiers in Immunology.2025;[Epub] CrossRef
NTRK-rearranged spindle cell neoplasm of the female genital tract: case report and literature review
Lulu Feng, Lei Li, Yanmei He, Wei Jiang
Frontiers in Oncology.2025;[Epub] CrossRef
Uterine Stroma-Derived Tumors and the Extracellular Matrix: A Comparative Review of Benign and Malignant Pathologies
Maria Marmara, Thomas Vrekoussis, Fanourios Makrygiannakis, Dragana Nikitovic, Aikaterini Berdiaki
Cancers.2025; 17(21): 3501. CrossRef
Genomics of uterine malignancies and the potential of precision medicine
Joseph Polidano, Andrew Jarratt, Clare L. Scott, Holly E. Barker
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival
Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai
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Single-cell RNA-seq reveals FGF12 as a prognostic biomarker in low-grade endometrial stromal sarcoma
Yu Miao, Meng Dong, Qiyin Zhou, Julia Thiel, Na Li, Ying Cai, Dan Yuan, Haitao Wang, Su-Han Jin, Hua Yang, Jinjing Wang, Benjamin Frey, Udo S. Gaipl, Hu Ma, Jian-Guo Zhou
Frontiers in Immunology.2024;[Epub] CrossRef
High-Grade Endometrial Mesenchymal Sarcoma: Current Status and Future Trends
Lushuang Zhang, Liubiqi Zhao
Clinical Journal of Obstetrics and Gynecology.2023; 6(3): 132. CrossRef

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Hematologic malignancy

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia: Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim; Cancer Res Treat. 2023;55(3):1011-1022. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1407

Abstract PDF PubReader ePub

Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP^in-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIP^in-f CEBPA, and 28 had non-bZIP^in-f CEBPA. In the multivariate analysis, patients with NPM1^mut, those with bZIP^in-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITD^mut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP^in-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITD^pos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPA^dm), bZIP^in-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP^in-f CEBPA. Of 50 patients with bZIP^in-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIP^in-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIP^in-f CEBPA was associated with favorable outcomes in patients with CEBPA^dm. However, some mutations accompanying bZIP^in-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP^in-f CEBPA.

Citations

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Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia
Li‐Xin Wu, Ming‐Yue Liao, Ming‐Yue Zhao, Nan Yan, Ping Zhang, Li‐Xia Liu, Jia‐Yue Qin, Shan‐Bo Cao, Jia Feng, Qian Jiang, Ying‐Jun Chang, Lan‐Ping Xu, Xiao‐Hui Zhang, Xiao‐Jun Huang, Hao Jiang, Hong‐Yu Zhang, Guo‐Rui Ruan
British Journal of Haematology.2026; 208(1): 170. CrossRef
CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
Blood Advances.2024; 8(6): 1487. CrossRef
CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
Blood Cancer Journal.2024;[Epub] CrossRef
Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
International Journal of Laboratory Hematology.2023; 45(6): 833. CrossRef

8,597 View
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Lung and Thoracic cancer

Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer: Rongxin Liao, Kehong Chen, Jinjin Li, Hengqiu He, Guangming Yi, Mingfeng Huang, Rongrong Chen, Lu Shen, Xiaoyue Zhang, Zaicheng Xu, Zhenzhou Yang, Yuan Peng; Cancer Res Treat. 2023;55(3):814-831. Published online January 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1315

Abstract PDF Supplementary Material PubReader ePub

Purpose
Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.
Materials and Methods
We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.
Results
We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation.
Conclusion
Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

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To ablate or not to ablate? Outcomes of local ablative treatments (LAT) for oncogene addicted (OA) oligo-metastatic (OM) non-small cell lung cancer (NSCLC): A systematic review
Fabrizio Citarella, Cristina Fragale, Matteo Fiorenti, Maria Luisa Di Guglielmo, Noemi Mindicini, Alessio Cortellini, Alessandro Russo, Giuseppe Bronte
Critical Reviews in Oncology/Hematology.2026; 218: 105096. CrossRef
Frequency and Prognostic Impact of Local Ablation Therapy for Oligoprogression in Non‐Small Cell Lung Cancer
Daisuke Morinaga, Jun Sakakibara‐Konishi, Ryohei Kamada, Masahiro Kashima, Kosuke Tsuji, Shotaro Ito, Megumi Furuta, Tetsuaki Shoji, Yuta Takashima, Hidenori Kitai, Yasuyuki Ikezawa, Hiroshi Taguchi, Tatsuya Kato, Yoshiki Shinomiya, Kanako C Hatanaka, Yut
Thoracic Cancer.2025;[Epub] CrossRef
Insights on Oligometastatic Non-Small-Cell Lung Cancer
Augusto Valdivia, Pau Mascaro-Baselga, Clara Salva-de Torres, Abraham Geng-Cahuayme, Sara Torresan, Jesus Yaringaño, Ilaria Priano, Patricia Iranzo, Nuria Pardo, Laura Masfarre, Oriol Mirallas, Karen Farfan, Susana Cedres, Pedro Rocha, Alex Martinez-Marti
Cancers.2025; 17(15): 2451. CrossRef
Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications
Mandy Jongbloed, Martina Bortolot, Leonard Wee, Jarno W.J. Huijs, Murillo Bellezo, Rianne D.W. Vaes, Frank Aboubakar Nana, Koen J. Hartemink, Dirk K.M. De Ruysscher, Lizza E.L. Hendriks
JTO Clinical and Research Reports.2024; 5(12): 100740. CrossRef
Genomic characteristics of PD-L1-Induced resistance to EGFR-TKIs in lung adenocarcinoma
Guangming Yi, Fanghao Cai, Liangzhong Liu, Rongxin Liao, Xuan Jiang, Zhenzhou Yang, Xiaoyue Zhang
Future Oncology.2024; 20(40): 3477. CrossRef

7,496 View
218 Download
7 Web of Science
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