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

  • Authors:
    • Li Li
    • Xiaosong Rao
    • Zhaohong Wen
    • Xiaosheng Ding
    • Xiangyi Wang
    • Weiran Xu
    • Chao Meng
    • Yuting Yi
    • Yanfang Guan
    • Yongshen Chen
    • Jiayin Wang
    • Liang Jun

  • View Affiliations

  • Published online on: February 5, 2020     https://doi.org/10.3892/ol.2020.11372
  • Pages: 2739-2748

  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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April-2020
Volume 19 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Li L, Rao X, Wen Z, Ding X, Wang X, Xu W, Meng C, Yi Y, Guan Y, Chen Y, Chen Y, et al: Implications of driver genes associated with a high tumor mutation burden identified using next‑generation sequencing on immunotherapy in hepatocellular carcinoma. Oncol Lett 19: 2739-2748, 2020.
APA
Li, L., Rao, X., Wen, Z., Ding, X., Wang, X., Xu, W. ... Jun, L. (2020). Implications of driver genes associated with a high tumor mutation burden identified using next‑generation sequencing on immunotherapy in hepatocellular carcinoma. Oncology Letters, 19, 2739-2748. https://doi.org/10.3892/ol.2020.11372
MLA
Li, L., Rao, X., Wen, Z., Ding, X., Wang, X., Xu, W., Meng, C., Yi, Y., Guan, Y., Chen, Y., Wang, J., Jun, L."Implications of driver genes associated with a high tumor mutation burden identified using next‑generation sequencing on immunotherapy in hepatocellular carcinoma". Oncology Letters 19.4 (2020): 2739-2748.
Chicago
Li, L., Rao, X., Wen, Z., Ding, X., Wang, X., Xu, W., Meng, C., Yi, Y., Guan, Y., Chen, Y., Wang, J., Jun, L."Implications of driver genes associated with a high tumor mutation burden identified using next‑generation sequencing on immunotherapy in hepatocellular carcinoma". Oncology Letters 19, no. 4 (2020): 2739-2748. https://doi.org/10.3892/ol.2020.11372