Implications of driver genes associated with a high tumor mutation burden identified using next-generation sequencing on immunotherapy in hepatocellular carcinoma

Immune checkpoint blockade (ICB) therapy is a treatment strategy for hepatocellular carcinoma (HCC); however, its clinical efficacy is limited to a select subset of patients. Next-generation sequencing has identified the value of tumor mutation burden (TMB) as a predictor for ICB efficacy in multipl...

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Bibliographic Details
Published in:Oncology letters 2020-04, Vol.19 (4), p.2739-2748
Main Authors: Li, Li, Rao, Xiaosong, Wen, Zhaohong, Ding, Xiaosheng, Wang, Xiangyi, Xu, Weiran, Meng, Chao, Yi, Yuting, Guan, Yanfang, Chen, Yongshen, Wang, Jiayin, Jun, Liang
Format: Article
Language:English
Subjects:
Biomarkers
Cancer treatment
Deoxyribonucleic acid
DNA
Drug therapy
EDTA
Gene mutation
Genes
Genetic aspects
Genomes
Genomics
Health aspects
Hepatocellular carcinoma
Immunotherapy
Kinases
Liver cancer
Medical prognosis
Melanoma
Mutation
Proteins
Telomerase
Tumor proteins
Tumors
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Summary:Immune checkpoint blockade (ICB) therapy is a treatment strategy for hepatocellular carcinoma (HCC); however, its clinical efficacy is limited to a select subset of patients. Next-generation sequencing has identified the value of tumor mutation burden (TMB) as a predictor for ICB efficacy in multiple types of tumor, including HCC. Specific driver gene mutations may be indicative of a high TMB (TMB-H) and analysis of such mutations may provide novel insights into the underlying mechanisms of TMB-H and potential therapeutic strategies. In the present study, a hybridization-capture method was used to target 1.45 Mb of the genomic sequence (coding sequence, 1 Mb), analyzing the somatic mutation landscape of 81 HCC tumor samples. Mutations in five genes were significantly associated with TMB-H, including mutations in tumor protein 53 (TP53), Catenin 1 (CTNNB1), AT-rich interactive domain-containing protein 1A (ARID1A), myeloid/lymphoid or mixed-lineage leukemia (MLL) and nuclear receptor co-repressor 1 (NCOR1). Further analysis using The Cancer Genome Atlas Liver Hepatocellular Carcinoma database showed that TP53, CTNNB1 and MLL mutations were positively correlated with TMB-H. Meanwhile, mutations in ARID1A, TP53 and MLL were associated with poor overall survival of patients with HCC. Overall, TMB-H and associated driver gene mutations may have potential as predictive biomarkers of ICB therapy efficacy for treatment of patients with HCC.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2020.11372