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 639×, 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.