Cancer Research and Treatment

Original Articles

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

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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.

Citations

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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
Long-Read Nanopore Sequencing Enhances BRCA1/2 Variant Detection Compared to Ion Torrent Analysis
Nada El Makhzen, Brahim El Hejjioui, Badreddine ElMakhzen, Abdelhamid Bouramtane, Sanae Bennis, Laila Bouguenouch, Hugues Abriel
The Journal of Molecular Diagnostics.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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CNS cancer

Detection of TERT Promoter Mutations Using Targeted Next-Generation Sequencing: Overcoming GC Bias through Trial and Error: Hyunwoo Lee, Boram Lee, Deok Geun Kim, Yoon Ah Cho, Jung-Sun Kim, Yeon-Lim Suh; Cancer Res Treat. 2022;54(1):75-83. Published online May 3, 2021; DOI: https://doi.org/10.4143/crt.2021.107

Abstract PDF Supplementary Material PubReader ePub

Purpose
Detection of telomerase reverse transcriptase (TERT) promoter mutations is a crucial process in the integrated diagnosis of glioblastomas. However, the TERT promoter region is difficult to amplify because of its high guanine-cytosine (GC) content (> 80%). This study aimed to analyze the capturing of TERT mutations by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tissues.
Materials and Methods
We compared the detection rate of TERT mutations between targeted NGS and Sanger sequencing in 25 cases of isocitrate dehydrgenase (IDH)-wildtype glioblastomas and 10 cases of non-neoplastic gastric tissues. Our customized panel consisted of 232 essential glioma-associated genes.
Results
Sanger sequencing detected TERT mutations in 17 out of 25 glioblastomas, but all TERT mutations were missed by targeted NGS. After the manual visualization of the NGS data using an integrative genomics viewer, 16 cases showed a TERT mutation with a very low read depth (mean, 21.59; median, 25), which revealed false-negative results using auto-filtering. We optimized our customized panel by extending the length of oligonucleotide baits and increasing the number of baits spanning the coverage of the TERT promoter, which did not amplify well due to the high GC content.
Conclusion
Our study confirmed that it is crucial to consider the recognition of molecular bias and to carefully interpret NGS data.

Citations

Citations to this article as recorded by

Development of a novel MSRE-dPCR assay for non-invasive prenatal testing of trisomy 21
Chunmao Lin, Tan Wang, Boyang Han, Chenyu Jiang, Yang Ding, Huancai Yin, Liang Gao, Jian Yin
Analytical Methods.2026; 18(5): 1116. CrossRef
Development and Performance Validation of a Comprehensive Liquid Biopsy Genotyping Panel for Pan-cancer Analysis
Seoyoung Lim, Kwang Seob Lee, Dongju Won, Sung Hyun Seo, Seung-Tae Lee, Jong Rak Choi, Jieun Seo, Saeam Shin
Annals of Laboratory Medicine.2026; 46(2): 210. CrossRef
Digital polymerase chain reaction detection of telomerase reverse transcriptase promoter mutations in hepatitis B virus related hepatocellular carcinoma
Shuai Shao, Yu Xiong, Mo-Wei Kong, Yang Yu, Chun-Xiang Zhang
World Journal of Gastrointestinal Oncology.2026;[Epub] CrossRef
Modernizing Neuro-Oncology: The Impact of Imaging, Liquid Biopsies, and AI on Diagnosis and Treatment
John Rafanan, Nabih Ghani, Sarah Kazemeini, Ahmed Nadeem-Tariq, Ryan Shih, Thomas A. Vida
International Journal of Molecular Sciences.2025; 26(3): 917. CrossRef
A Concordance Study among 26 NGS Laboratories Participating in the NCI Molecular Analysis for Therapy Choice Clinical Trial
Linda K. Zane, Laura M. Yee, Ting-Chia Chang, Jeffrey Sklar, Guangxiao Yang, Jia Di Wen, Peining Li, Robin Harrington, David J. Sims, Kneshay Harper, Jeffrey M. Trent, Janine R. LoBello, Szabolcs Szelinger, Kasey Benson, Jia Zeng, Kelsey Poorman, Danbin X
Clinical Cancer Research.2025; 31(16): 3512. CrossRef
Clinical Feasibility of Circulating Tumor DNA in Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab
Sohyun Hwang, Dong Jun Shin, Beodeul Kang, Haeyoun Kang, Sung Hwan Lee, Jung Sun Kim, Je-Gun Joung, Suyog Jain, Steven Olsen, Lars Becker, Richard S. Finn, Josep M. Llovet, Gwangil Kim, Chan Kim, Hong Jae Chon
Liver Cancer.2025; : 1. CrossRef
Quality metrics for enhanced performance of an NGS panel using single-vial amplification technology
Subit Barua, Susan Hsiao, Emily Clancy, Christopher Freeman, Mahesh Mansukhani, Helen Fernandes
Journal of Clinical Pathology.2024; 77(1): 46. CrossRef
Diagnostic utility of genetic alterations in distinguishing IDH‐wildtype glioblastoma from lower‐grade gliomas: Insight from next‐generation sequencing analysis of 479 cases
Boram Lee, Soohyun Hwang, Hyunsik Bae, Kyue‐Hee Choi, Yeon‐Lim Suh
Brain Pathology.2024;[Epub] CrossRef
Novel method for detecting frequent TERT promoter hot spot mutations in bladder cancer samples
Ákos Kovács, Farkas Sükösd, Levente Kuthi, Imre M. Boros, Balázs Vedelek
Clinical and Experimental Medicine.2024;[Epub] CrossRef
Changes in Mutations of Cell-Free DNA and Liver Tumor Tissue in Patients with Advanced Hepatocellular Carcinoma before and after Introduction of Lenvatinib
Mio Tsuruoka, Masashi Ninomiya, Jun Inoue, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Atsushi Masamune
Oncology.2024; 102(12): 1072. CrossRef
Melanoma genomics – will we go beyond BRAF in clinics?
Justyna Mirek, Wiesław Bal, Magdalena Olbryt
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Deep Learning Prediction of TERT Promoter Mutation Status in Thyroid Cancer Using Histologic Images
Jinhee Kim, Seokhwan Ko, Moonsik Kim, Nora Jee-Young Park, Hyungsoo Han, Junghwan Cho, Ji Young Park
Medicina.2023; 59(3): 536. CrossRef
Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules
Guodong Fu, Ronald S. Chazen, Eric Monteiro, Allan Vescan, Jeremy L. Freeman, Ian J. Witterick, Christina MacMillan
JAMA Network Open.2023; 6(7): e2323500. CrossRef
Molecular Biomarkers and Recent Liquid Biopsy Testing Progress: A Review of the Application of Biosensors for the Diagnosis of Gliomas
Yuanbin Wu, Xuning Wang, Meng Zhang, Dongdong Wu
Molecules.2023; 28(15): 5660. CrossRef
Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas
Gábor Bedics, Péter Szőke, Bence Bátai, Tibor Nagy, Gergő Papp, Noémi Kránitz, Hajnalka Rajnai, Lilla Reiniger, Csaba Bödör, Bálint Scheich
Scientific Reports.2023;[Epub] CrossRef

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17 Web of Science
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Gastrointestinal cancer

Evaluation of the American Joint Committee on Cancer (AJCC) 8th Edition Staging System for Hepatocellular Carcinoma in 1,008 Patients with Curative Resection: Sujin Park, Sangjoon Choi, Yoon Ah Cho, Dong Hyun Sinn, Jong Man Kim, Cheol-Keun Park, Sang Yun Ha; Cancer Res Treat. 2020;52(4):1145-1152. Published online April 28, 2020; DOI: https://doi.org/10.4143/crt.2020.208

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recently, the 8th edition staging system of the American Joint Committee on Cancer (AJCC) for hepatocellular carcinoma (HCC) was released, including a change in T category. We aimed to validate the new AJCC system.
Materials and Methods
The predictive value of the new AJCC was validated in comparison to the previous edition, in a total 1,008 patients who underwent curative resection for HCC as initial treatment.
Results
The 2-year area under the curve values for recurrence-free survival (RFS) and overall survival (OS) were comparable in the 7th and 8th editions. Stage migration was observed in 63 patients (6.3%); from T2 to T1a for 44 patients and from T3 to T4 for 19 patients. The RFS and OS were not different between T1a and T1b in the 8th edition. For solitary tumors ≤ 2 cm, those with microvascular invasion had lower RFS and OS values than those without although they were all classified as T1a in the 8th edition. Tumors involving a major branch of the portal or hepatic vein (T4 by the 8th edition and T3b by the 7th edition) had shorter RFS and OS than multifocal tumors, at least one of which was > 5 cm (T3 by the 8th edition and T3a by the 7th edition).
Conclusion
The AJCC 8th edition staging system for HCC showed comparable predictive performance to the 7th edition. It is desirable in a future revision to consider sub-stratification of solitary tumors ≤ 2 cm (T1a) depending on the presence of vascular invasion, which is not included in the 8th edition.

Citations

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Comparative effectiveness of the revised American Joint Committee on Cancer staging system
Chia-Wen Kao, Chun-Ju Chiang, Wen-Chung Lee
American Journal of Epidemiology.2025; 194(6): 1735. CrossRef
Improving Adherence of Young Male Patients with HBV Infection to the Regular Follow-Up via Mobile Healthcare Platform Might Be Cost-Effective to Decrease the Morbidity of Advanced Liver Cancer
Hao Liang, Min Yang, Dan Luo, Ya-Kun Wu
Patient Preference and Adherence.2024; Volume 18: 2581. CrossRef
Prognostic impact of tumor size on isolated hepatocellular carcinoma without vascular invasion may have age variance
Yi Zhang, Jun-Gang Zhang, Wei Yu, Lei Liang, Chun Wu, Cheng-Wu Zhang, Ya-Ming Xie, Dong-Sheng Huang, Ying Shi
Frontiers in Surgery.2023;[Epub] CrossRef
Advances in post-operative prognostic models for hepatocellular carcinoma
Ziqin He, Xiaomin She, Ziyu Liu, Xing Gao, Lu Lu, Julu Huang, Cheng Lu, Yan Lin, Rong Liang, Jiazhou Ye
Journal of Zhejiang University-SCIENCE B.2023; 24(3): 191. CrossRef
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Journal of Liver Cancer.2023; 23(1): 1. CrossRef
Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer
Yueh-Wei Liu, Wei-Feng Li, Fang-Ying Kuo, Hock-Liew Eng, Chih-Chi Wang, Chih-Che Lin, Chee-Chien Yong, Yi-Hao Yen
Langenbeck's Archives of Surgery.2023;[Epub] CrossRef
Perfusion parameters of triphasic computed tomography hold preoperative prediction value for microvascular invasion in hepatocellular carcinoma
Li Zhang, Guodong Pang, Jing Zhang, Zhenguo Yuan
Scientific Reports.2023;[Epub] CrossRef
AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma
Diwakar Suresh, Akshatha N. Srinivas, Akila Prashant, Suchitha Satish, Prashant Vishwanath, Suma M. Nataraj, Srinivas V. Koduru, Prasanna K. Santhekadur, Divya P. Kumar
Frontiers in Oncology.2023;[Epub] CrossRef
ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma
Yiyin Zhang, Jiaxi Cheng, Cheng Zhong, Qiming Xia, Yirun Li, Peng Chen, Xiaoxiao Fan, Qijiang Mao, Hui Lin, Defei Hong
Frontiers in Oncology.2022;[Epub] CrossRef
Efficacy of Postoperative Adjuvant Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma Patients With Microscopic Portal Vein Invasion
Yiwen Qiu, Yi Yang, Tao Wang, Shu Shen, Wentao Wang
Frontiers in Oncology.2022;[Epub] CrossRef
Nomogram Based on Inflammatory Biomarkers to Predict the Recurrence of Hepatocellular Carcinoma—A Multicentre Experience
Zehao Zheng, Renguo Guan, Yiping Zou, Zhixiang Jian, Ye Lin, Rongping Guo, Haosheng Jin
Journal of Inflammation Research.2022; Volume 15: 5089. CrossRef
CSTF2 Acts as a Prognostic Marker Correlated with Immune Infiltration in Hepatocellular Carcinoma
Wang Zhang, Yipeng Wan, Yue Zhang, Qi Liu, Xuan Zhu
Cancer Management and Research.2022; Volume 14: 2691. CrossRef
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Clinical and Molecular Hepatology.2022; 28(4): 583. CrossRef
Revisiting Surgical Strategies for Hepatocellular Carcinoma With Microvascular Invasion
Er-lei Zhang, Qi Cheng, Zhi-yong Huang, Wei Dong
Frontiers in Oncology.2021;[Epub] CrossRef
Two-Trait Predictor of Venous Invasion on Contrast-Enhanced CT as a Preoperative Predictor of Outcomes for Early-Stage Hepatocellular Carcinoma After Hepatectomy
Xinming Li, Xuchang Zhang, Zhipeng Li, Chuanmiao Xie, Shuping Qin, Meng Yan, Qiying Ke, Xuan Jin, Ting Lin, Muyao Zhou, Wen Liang, Zhendong Qi, Zhijun Geng, Xianyue Quan
Frontiers in Oncology.2021;[Epub] CrossRef
Construction and Validation of an Immune Cell Signature Score to Evaluate Prognosis and Therapeutic Efficacy in Hepatocellular Carcinoma
Linfeng Xu, Xingxing Jian, Zhenhao Liu, Jingjing Zhao, Siwen Zhang, Yong Lin, Lu Xie
Frontiers in Genetics.2021;[Epub] CrossRef
Up-to-date Knowledge on the Pathological Diagnosis of Hepatocellular Carcinoma
Ji Hae Nahm, Young Nyun Park
The Korean Journal of Gastroenterology.2021; 78(5): 268. CrossRef

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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection: Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon; Cancer Res Treat. 2019;51(3):1052-1063. Published online October 24, 2018; DOI: https://doi.org/10.4143/crt.2018.411

Abstract PDF Supplementary Material PubReader ePub

Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

Citations

Citations to this article as recorded by

TrkA Expression as a Novel Prognostic Biomarker in Oral Squamous Cell Carcinoma
Aleksandra Ciarka, Filip Skowronek, Przemysław Miłosz, Michał Kunc, Robert Burdach, Monika Sakowicz-Burkiewicz, Barbara Jereczek-Fossa, Anna Starzyńska, Rafał Pęksa
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Role of NTRK Fusion Genes in the Tumor Immune Microenvironment of HPV (+/−) Cervical Cancer
Qiongying Wang, Chan Zhang, Shijia Liu, Wangshu Li, Wenjuan Wei, Aziz ur Rehman Aziz, Han Lu, Daqing Wang
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NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population
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Dentistry Journal.2024; 12(10): 327. CrossRef
Accuracy of magnetic resonance imaging in the assessment of depth of invasion in tongue carcinoma: A systematic review and meta-analysis
Kondajji Ramachandra Vijayalakshmi, Vanshika Jain
National Journal of Maxillofacial Surgery.2023; 14(3): 341. CrossRef
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Molecular Cancer Research.2021; 19(1): 14. CrossRef
Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer
Zijian Chen, Zenghong Huang, Yanxin Luo, Qi Zou, Liangliang Bai, Guannan Tang, Xiaolin Wang, Guangwen Cao, Meijin Huang, Jun Xiang, Huichuan Yu
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Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park, Sang Yun Ha
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Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro‐oncogenic phenotype in HNSCC
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NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
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