Cancer Research and Treatment

Original Articles

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, Sung Hee Lim, Seung Tae Kim, Jung Yong Hong, Se Hoon Park, Joon Oh Park, Kyoung-Mee Kim, Jeeyun Lee; Received June 17, 2024 Accepted January 21, 2025 Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2024.564 [Accepted]

Abstract PDF: 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 8 (0.2%) had EGFR fusion. All 175 patients with EGFR amplifications had microsatellite-stable (MSS) 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 eleven (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

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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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

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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.

Citations

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The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance
Ahmad Dawalibi, Mohamad Bakir, Khalid S. Mohammad
Cancer Drug Resistance.2025;[Epub] 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
Frontiers in Bioscience-Landmark.2024;[Epub] CrossRef
Primary mucinous cystadenocarcinoma of the breast: A case report and literature review
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.

Citations

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Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
Journal of Hepatology.2025; 82(4): 649. CrossRef
Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization
Rattanaporn Jaidee, Apinya Jusakul, Piman Pocasap, Veerapol Kukongviriyapan, Laddawan Senggunprai, Auemduan Prawan, Watcharin Loilome, Attapol Titapun, Apiwat Jareanrat, Vasin Thanasukarn, Natcha Khuntikeo, Nisana Namwat, Yaovalux Chamgramol, Malinee Than
Scientific Reports.2025;[Epub] CrossRef
Epidemiology and genomic features of biliary tract cancer and its unique features in Korea
Seonjeong Woo, Youngun Kim, Sohyun Hwang, Hong Jae Chon
Journal of Liver Cancer.2025; 25(1): 41. CrossRef
ARID1A in Gynecologic Precancers and Cancers
Jaida E. Morgan, Nishah Jaferi, Zainab Shonibare, Gloria S. Huang
Reproductive Sciences.2024; 31(8): 2150. CrossRef
Genomic analysis of bladder urothelial carcinoma with osteoclast‑like giant cells: A case report
Koji Kameyama, Kosuke Mizutani, Tetsuya Yamada, Seiji Sugiyama, Shingo Kamei, Shigeaki Yokoi, Kengo Matsunaga, Koseki Hirade, Yasutaka Kato, Hiroshi Nishihara, Satoshi Ishihara, Takashi Deguchi
Molecular and Clinical Oncology.2024;[Epub] CrossRef
A mutational signature and ARID1A mutation associated with outcome in hepatocellular carcinoma
Wei Zhou, Hao Chi, Xiaohu Zhao, Guangrong Tao, Jianhe Gan
Clinical and Translational Oncology.2024; 27(3): 1166. CrossRef
Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors
Jiumei Zhao, Jing Zhu, Yu Tang, Kepu Zheng, Ziwei Li
Frontiers in Oncology.2024;[Epub] CrossRef
The role of ARID1A in malignant neoplasms of the female reproductive system: a modern view on diagnostic and therapeutic opportunities
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.2024;[Epub] CrossRef

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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.

Citations

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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

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General

Validation and Clinical Application of ONCOaccuPanel for Targeted Next-Generation Sequencing of Solid Tumors: Moonsik Kim, Changseon Lee, Juyeon Hong, Juhee Kim, Ji Yun Jeong, Nora Jee-Young Park, Ji-Eun Kim, Ji Young Park; Cancer Res Treat. 2023;55(2):429-441. Published online November 25, 2022; DOI: https://doi.org/10.4143/crt.2022.891

Abstract PDF Supplementary Material PubReader ePub

Purpose
Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors.
Materials and Methods
We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel.
Results
Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability–high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively.
Conclusion
ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.

Citations

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Risk prediction criteria for the primary hepatic perivascular epithelioid cell tumour family, including angiomyolipoma: analysis of 132 cases with a literature review
Youngeun Yoo, Jihun Kim, In Hye Song
Histopathology.2025; 86(6): 979. CrossRef
Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma
In Hye Song, Bokyung Ahn, Young Soo Park, Deok Hoon Kim, Seung-Mo Hong
Cancer Research and Treatment.2025; 57(2): 492. CrossRef
Primary Solid Pseudopapillary Tumor of the Ovary: A Case Report and Review of the Literature
Juhun Lee, Seung Ho Song, In Hee Lee, Dong Ja Kim, Hyun Jung Lee
Journal of Clinical Medicine.2024; 13(10): 2791. CrossRef
Genome-scale mutational signature analysis in archived fixed tissues
Bérénice Chavanel, François Virard, Vincent Cahais, Claire Renard, Cécilia Sirand, Kim M. Smits, Leo J. Schouten, Béatrice Fervers, Barbara Charbotel, Behnoush Abedi-Ardekani, Michael Korenjak, Jiri Zavadil
Mutation Research - Reviews in Mutation Research.2024; 794: 108512. CrossRef
Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer
Jinahn Jeong, Deokhoon Kim, Yeon-Mi Ryu, Ja-Min Park, Sun Young Yoon, Bokyung Ahn, Gi Hwan Kim, Se Un Jeong, Hyun-Jung Sung, Yong Il Lee, Sang-Yeob Kim, Yong Mee Cho
Journal of Pathology and Translational Medicine.2024; 58(5): 229. CrossRef
CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas
Sang Hyuk Lee, Tae Gyu Kim, Kyeong Hwa Ryu, Seok Hyun Kim, Young Zoon Kim
Biomedicines.2024; 12(10): 2256. CrossRef
Comparison of immunohistochemistry and next-generation sequencing results in oncogenic PTEN missense mutations
Moonsik Kim, Jinhee Kim, An Na Seo, Ji Yun Jeong, Nora Jee-Young Park, Gun Oh Chong, Dae Gy Hong, Ji Young Park
Pathology - Research and Practice.2023; 251: 154879. CrossRef
BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy
Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim
Journal of Pathology and Translational Medicine.2023; 57(6): 323. CrossRef
Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma
Hyeon Yeong Jeong, Won Jun Suh, Seung Hwan Kim, Taek Min Nam, Ji Hwan Jang, Kyu Hong Kim, Seok Hyun Kim, Young Zoon Kim
Cancers.2023; 16(1): 88. CrossRef

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Lung and Thoracic cancer

Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing: Beung-Chul Ahn, Ye-Jeong Han, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim; Cancer Res Treat. 2023;55(2):488-497. Published online November 9, 2022; DOI: https://doi.org/10.4143/crt.2022.359

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents.
Materials and Methods
Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed.
Results
The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively.
Conclusion
Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

Citations

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Targeted therapy for older patients with an oncogene driven non-small cell lung cancer: Recommendations from a SIOG expert group
L. Decoster, D.R. Camidge, J.A. Fletcher, A. Addeo, A. Greystoke, K. Kantilal, L.Bigay Game, R. Kanesvaran, F. Gomes
Lung Cancer.2025; 200: 108087. CrossRef
HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study
John V. Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto
Journal of Clinical Oncology.2025; 43(11): 1337. CrossRef
Targeting HER2 in lung cancers: Evolving treatment landscape and drug development strategies
Daniel Reinhorn, Mor Moskovitz, William D. Tap, Bob T. Li
Cancer.2025;[Epub] CrossRef
Real-world therapeutic strategies and survival outcomes in advanced HER2-mutant non-small cell lung cancer
Ruei-Lin Sun, Pei-Ya Liao, Ying-Ting Liao, Yi-Chen Yeh, Chi-Lu Chiang, Yuh-Min Chen, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Hsu-Ching Huang, Chia-I Shen, Yen-Han Tseng, Yen-Hsiang Huang, Yung-Hung Luo, Tsung-Ying Yang
Journal of the Chinese Medical Association.2025; 88(4): 307. CrossRef
Genomic and clinical characterization of HER2 exon 20 mutations in non-small cell lung cancer: insights from a multicenter study in South China
Yating Hou, Xingyang Xue, Zhuoyun Zhang, Dahai Mai, Wei Luo, Mingyu Zhou, Zichuan Liu, Yisheng Huang
BMC Cancer.2025;[Epub] CrossRef
Prognostic factors in non-metastatic HER2 ‘low’ and HER2 ‘negative’ breast cancer: single institute experience
Alper Türkel, Mutlu Doğan, Elif Sertesen, Cengiz Karaçin, Sultan Çiğdem Irkkan, Öztürk Ateş
Wiener klinische Wochenschrift.2024; 136(11-12): 340. CrossRef
Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non–Small Cell Lung Cancer: Implications for Precision Medicine
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
Modern Pathology.2024; 37(6): 100490. CrossRef
Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations
Meng Hu, Congying Zhong, Jiabing Wang, JinQin Chen, Tao Zhou
Frontiers in Immunology.2024;[Epub] CrossRef
Efficacy of chemotherapy plus immune checkpoint inhibitors in patients with non-small cell lung cancer who have rare oncogenic driver mutations: a retrospective analysis
Teppei Yamaguchi, Junichi Shimizu, Reiko Matsuzawa, Naohiro Watanabe, Yoshitsugu Horio, Yutaka Fujiwara
BMC Cancer.2024;[Epub] CrossRef
Antibody–Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases
David J. H. Bian, Sara F. Cohen, Anna-Maria Lazaratos, Nathaniel Bouganim, Matthew Dankner
Current Oncology.2024; 31(10): 6314. CrossRef
Real-World Clinical Outcomes for Patients with EGFR and HER2 Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer
Kelly Li, Ian Bosdet, Stephen Yip, Cheryl Ho, Janessa Laskin, Barbara Melosky, Ying Wang, Sophie Sun
Current Oncology.2023; 30(8): 7099. CrossRef

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Breast cancer

Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation: Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon-Ji Choi, Yeul Hong Kim, Kyong Hwa Park; Cancer Res Treat. 2023;55(1):155-166. Published online June 8, 2022; DOI: https://doi.org/10.4143/crt.2021.1567

Abstract PDF Supplementary Material PubReader ePub

Purpose
BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants.
Materials and Methods
Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity.
Results
A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w.
Conclusion
We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

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Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre
Baijaeek Sain, Arnab Gupta, Aruni Ghose, Sudip Halder, Vishal Mukherjee, Samir Bhattacharya, Radha Raman Mondal, Aditya Narayan Sen, Bijan Saha, Shravasti Roy, Stergios Boussios
Journal of Personalized Medicine.2023; 13(5): 866. CrossRef

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209 Download
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Gastrointestinal cancer

Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer: Jihoon Kang, Ji-Young Lee, Sunmin Lee, Danbee Kim, Jinyeong Lim, Ha Ra Jun, Seyeon Jeon, Young-Ae Kim, Hye Seon Park, Kyu-pyo Kim, Sung-Min Chun, Hee Jin Lee, Changhoon Yoo; Cancer Res Treat. 2023;55(1):219-230. Published online April 6, 2022; DOI: https://doi.org/10.4143/crt.2021.1166

Abstract PDF Supplementary Material PubReader ePub

Purpose
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

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The importance of preclinical models for cholangiocarcinoma drug discovery
Felix J. Krendl, Florian Primavesi, Rupert Oberhuber, Daniel Neureiter, Matthias Ocker, Dino Bekric, Tobias Kiesslich, Christian Mayr
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Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
Journal of Clinical Medicine.2024; 13(9): 2718. CrossRef

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General

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations: Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim; Cancer Res Treat. 2022;54(1):30-39. Published online May 20, 2021; DOI: https://doi.org/10.4143/crt.2021.218

Abstract PDF PubReader ePub

Purpose
K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods
Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results
In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion
The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

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Clinical Lung Cancer.2025;[Epub] CrossRef
Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
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Albrecht Stenzinger, Brian Cuffel, Noman Paracha, Eric Vail, Jesus Garcia-Foncillas, Clifford Goodman, Ulrik Lassen, Gilles Vassal, Sean D Sullivan
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Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
Cancer Research and Treatment.2022; 54(1): 1. CrossRef

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Gastrointestinal cancer

Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project: Youngwoo Lee, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Ah-reum Lim, Ju Won Kim, Yoon Ji Choi, Kyong Hwa Park, Yeul Hong Kim; Cancer Res Treat. 2021;53(1):123-130. Published online August 18, 2020; DOI: https://doi.org/10.4143/crt.2020.559

Abstract PDF Supplementary Material PubReader ePub

Purpose
Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations.
Materials and Methods
As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy.
Results
In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors.
Conclusion
K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

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Tumor mutational burden in colorectal cancer: Implications for treatment
Adriana Marques, Patrícia Cavaco, Carla Torre, Bruno Sepodes, João Rocha
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Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
BMC Cancer.2024;[Epub] CrossRef
PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
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Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations
Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Se
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Saleema Mehboob Ali, Yumna Adnan, Zubair Ahmad, Hasnain Ahmed Farooqui, Tabish Chawla, S. M. Adnan Ali
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Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
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Phase II study to investigate the efficacy of trastuzumab biosimilar (Herzuma®) plus treatment of physician's choice (TPC) in patients with heavily pretreated HER-2+ metastatic breast cancer (KCSG BR 18–14/KM10B)
Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Koung Jin Suh, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, Jae Ho Byun, Jin Hyun Park, Gyeong-Won L
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Aitor Rodríguez-Casanova, Aida Bao-Caamano, Ramón M. Lago-Lestón, Elena Brozos-Vázquez, Nicolás Costa-Fraga, Isabel Ferreirós-Vidal, Ihab Abdulkader, Yolanda Vidal-Insua, Francisca Vázquez Rivera, Sonia Candamio Folgar, Rafael López-López, Laura Muinelo-R
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Saikat Chowdhury, Matan Hofree, Kangyu Lin, Dipen Maru, Scott Kopetz, John Paul Shen
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Case Report

Seminal Vesicle Involvement by Carcinoma In Situ of the Bladder: Clonal Analysis Using Next-Generation Sequencing to Elucidate the Mechanism of Tumor Spread: Hyun Sik Park, Hyun Bin Shin, Myung-Shin Lee, Joo Heon Kim, Seon-Young Kim, Jinsung Park; Cancer Res Treat. 2020;52(4):1283-1287. Published online March 19, 2020; DOI: https://doi.org/10.4143/crt.2020.002

Abstract PDF Supplementary Material PubReader ePub: We present a rare case of urothelial carcinoma in situ (CIS), which invades the prostate and seminal vesicle (SV). A 70-year-old man underwent transurethral resection of bladder (TURB), and the pathologic examination revealed multiple CIS. Although the patient received intravesical bacillus Calmette-Guerin (BCG) therapy following TURB, recurrence of CIS was confirmed in the bladder and left distal ureter at 3 months following BCG. Radical cystectomy was performed due to BCG-refractory CIS. Microscopically, CIS was found throughout the mucosa of the bladder, left ureter, prostatic duct, and both SVs. Next-generation sequencing revealed significant differences in tumor clonality between bladder and SV CIS cells. Among 101 (bladder CIS) and 95 (SV CIS) somatic mutations, only two were shared, and only one gene (ARHGAP23) was common exon coding region gene. In conclusion, multicentric genetic changes, in line with the field-cancerization effect, may result in SV involvement by CIS of the bladder.

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Original Articles

Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine: Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti; Cancer Res Treat. 2018;50(2):356-365. Published online May 26, 2017; DOI: https://doi.org/10.4143/crt.2017.125

Abstract PDF Supplementary Material PubReader ePub

Purpose
Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease.
Materials and Methods
A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients’ peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants.
Results
Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR.
Conclusion
In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.

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Yingxi Mo, Jun Zhao, Ran Zhao, Yiying Huang, Ziyuan Liang, Xiaoying Zhou, Jiemei Chu, Xinli Pan, Siyu Duan, Shiman Chen, Liufang Mo, Bizhou Huang, Zhaozhang Huang, Jiale Wei, Qian Zheng, Wenqi Luo
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Pawel Rajwa, Nicolai A. Huebner, Dadjar I. Hostermann, Nico C. Grossmann, Victor M. Schuettfort, Stephan Korn, Fahad Quhal, Frederik König, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Reza Sari Motlagh, Takafumi Yanagisawa, Abdulmajeed Aydh, Piot
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Kasturi Bhattacharjee, Moumita Nath, Yashmin Choudhury
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International Journal of Oncology.2018;[Epub] CrossRef

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Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2: Sang Mee Hwang, Ki Chan Lee, Min Seob Lee, Kyoung Un Park; Cancer Res Treat. 2018;50(1):255-264. Published online April 7, 2017; DOI: https://doi.org/10.4143/crt.2017.062

Abstract PDF Supplementary Material PubReader ePub

Purpose
Transition to next generation sequencing (NGS) for BRCA1/BRCA2 analysis in clinical laboratories is ongoing but different platforms and/or data analysis pipelines give different results resulting in difficulties in implementation. We have evaluated the Ion Personal Genome Machine (PGM) Platforms (Ion PGM, Ion PGM Dx, Thermo Fisher Scientific) for the analysis of BRCA1/2.
Materials and Methods
The results of Ion PGM with OTG-snpcaller, a pipeline based on Torrent mapping alignment program and Genome Analysis Toolkit, from 75 clinical samples and 14 reference DNA samples were compared with Sanger sequencing for BRCA1/BRCA2. Ten clinical samples and 14 reference DNA samples were additionally sequenced by Ion PGM Dx with Torrent Suite.
Results
Fifty types of variants including 18 pathogenic or variants of unknown significance were identified from 75 clinical samples and known variants of the reference samples were confirmed by Sanger sequencing and/or NGS. One false-negative results were present for Ion PGM/OTG-snpcaller for an indel variant misidentified as a single nucleotide variant. However, eight discordant results were present for Ion PGM Dx/Torrent Suite with both falsepositive and -negative results. A 40-bp deletion, a 4-bp deletion and a 1-bp deletion variant was not called and a false-positive deletion was identified. Four other variants were misidentified as another variant.
Conclusion
Ion PGM/OTG-snpcaller showed acceptable performance with good concordance with Sanger sequencing. However, Ion PGM Dx/Torrent Suite showed many discrepant results not suitable for use in a clinical laboratory, requiring further optimization of the data analysis for calling variants.

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Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer: Dalyong Kim, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Sung-Min Chun, Jihun Kim, Se Jin Jang, Tae Won Kim; Cancer Res Treat. 2017;49(1):37-43. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.069

Abstract PDF PubReader ePub

Purpose
Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RASmutational analysis using a high -throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing.
Materials and Methods
Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status.
Results
The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88).
Conclusion
Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.

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Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
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Review Article

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers: Yongjun Cha, Sheehyun Kim, Sae-Won Han; Cancer Res Treat. 2023;55(2):367-384.; DOI: https://doi.org/10.4143/crt.2023.446

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Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

Citations

Citations to this article as recorded by

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