Somatic mutation profiling of liver and biliary cancer by targeted next generation sequencing

Zhang,Bo‑Lun; Ji,Xu; Yu,Ling‑Xiang; Gao,Yuan; Xiao,Chao‑Hui; Liu,Jia; Zhao,De‑Xi; Le,Yi; Diao,Guang‑Hao; Sun,Jia‑Yi; Li,Gao‑Hua; Lei,Guang‑Lin; Yu,Peng; Wang,Rui‑Lan; Wu,Jian‑Zhong; Yang,Peng‑Hui; Yan,Jin; Li,Jing‑Yu; Xu,Jia‑Jia; Zhang,Shao‑Geng; Tian,Hu

doi:10.3892/ol.2018.9371

Somatic mutation profiling of liver and biliary cancer by targeted next generation sequencing

Authors:
- Bo‑Lun Zhang
- Xu Ji
- Ling‑Xiang Yu
- Yuan Gao
- Chao‑Hui Xiao
- Jia Liu
- De‑Xi Zhao
- Yi Le
- Guang‑Hao Diao
- Jia‑Yi Sun
- Gao‑Hua Li
- Guang‑Lin Lei
- Peng Yu
- Rui‑Lan Wang
- Jian‑Zhong Wu
- Peng‑Hui Yang
- Jin Yan
- Jing‑Yu Li
- Jia‑Jia Xu
- Shao‑Geng Zhang
- Hu Tian
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Affiliations: Department of General Surgery, Clinical Medical College of Weifang Medical University, Weifang, Shandong 261042, P.R. China, Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing 100039, P.R. China, Institute of Precision Medicine, 3D Medicines, Inc., Shanghai 201114, P.R. China, Department of Hepatobiliary Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
Published online on: August 29, 2018 https://doi.org/10.3892/ol.2018.9371
Pages: 6003-6012

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Abstract

Liver and biliary cancers are highly lethal cancer types lacking effective treatments. The somatic mutations, particularly those with low mutant allele frequencies, in Chinese patients with liver and biliary cancer have not been profiled, and the frequency of patients benefiting from targeted therapy has not been studied. The present study evaluated the tumor tissues of 45 Chinese patients with hepatocellular carcinoma (HCC) and 12 Chinese patients with biliary tract cancer (BTC) by targeted next generation sequencing, with an average coverage of 639x, to identify alterations in 372 cancer‑related genes. A total of 263 variants were identified in 139 genes, with 85.6% of these variants not previously reported in the Catalogue Of Somatic Mutations In Cancer database, and the mutation profile was different from the current datasets, including The Cancer Genome Atlas dataset and the National Cancer Center Japan (NCC_JP) dataset. Patients with hepatitis B virus (HBV) infection harbored more mutations than those without HBV infection, and the mutations in HBV carriers occurred preferentially in genes involved in vascular endothelial growth factor signaling pathways. Mutations in fibroblast growth factor and RAS signaling pathways were enriched in patients with cirrhosis, and alterations in interleukin and transforming growth factor signaling pathways were more frequently identified in individuals with abnormal bilirubin expression. Of all the patients, 7% exhibited variants in the target of sorafenib, and 42% harbored variants in the targets of drugs that have been approved to treat other types of cancer. These findings indicate diverse HCC/BTC variants patterns in different populations, and that the mutation load and patterns are correlated with clinical features. Further clinical studies are now warranted to evaluate the efficacies of other targeted drugs besides sorafenib in the treatment of patients with liver and biliary cancer.

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