- General
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Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing
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Hai-Yun Wang, Ling Deng, Ying-Qing Li, Xiao Zhang, Ya-Kang Long, Xu Zhang, Yan-Fen Feng, Yuan He, Tao Tang, Xin-Hua Yang, Fang Wang
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Cancer Res Treat. 2021;53(4):973-982. Published online February 18, 2021
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DOI: https://doi.org/10.4143/crt.2020.798
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 Abstract
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- Purpose
Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice.
Materials and Methods
TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate.
Results
The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs.
Conclusion
Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.
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Citations
Citations to this article as recorded by  - Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study
Ling Deng, Hai‐Yun Wang, Chun‐Fang Hu, Xiao‐Yun Liu, Kuntai Jiang, Juan‐Juan Yong, Xiao‐Yan Wu, Kai‐Hua Guo, Fang Wang
Pigment Cell & Melanoma Research.2024; 37(3): 363. CrossRef - Genomic Features of Homologous Recombination Deficiency in Breast Cancer: Impact on Testing and Immunotherapy
Umer Ali, Sunitha Vungarala, Venkataswarup Tiriveedhi
Genes.2024; 15(2): 162. CrossRef - Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef - Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors
Hai-Yun Wang, Ye Liu, Ling Deng, Kuntai Jiang, Xin-Hua Yang, Xiao-Yan Wu, Kai-Hua Guo, Fang Wang
Cancer Cell International.2023;[Epub] CrossRef - Homologous recombination repair gene mutations as a predictive biomarker for immunotherapy in patients with advanced melanoma
Zhixuan You, Meng Lv, Xuanyu He, Yingqin Pan, Junfeng Ge, Xue Hu, Yating Zheng, Mengli Huang, Chengzhi Zhou, Changxuan You
Frontiers in Immunology.2022;[Epub] CrossRef - The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy
Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef - Maximizing Small Biopsy Patient Samples: Unified RNA-Seq Platform Assessment of over 120,000 Patient Biopsies
P. Sean Walsh, Yangyang Hao, Jie Ding, Jianghan Qu, Jonathan Wilde, Ruochen Jiang, Richard T. Kloos, Jing Huang, Giulia C. Kennedy
Journal of Personalized Medicine.2022; 13(1): 24. CrossRef
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