Abstract
The features and significance of somatic mutation profiles in hepatocellular carcinoma (HCC) have not been completely elucidated to date. In this study, 39 tumor specimens from HCC patients were collected for gene variation analysis by next-generation sequencing (NGS), and a correlation analysis between mutated genes and clinical characteristics was also conducted. The results were compared with genome data from cBioPortal database. Our study found that T > G/A > C transversions (Tv) and C > T/G > A transitions (Ti) were dominant. The sequence variations of TP53, MUC16, MUC12, MUC4 and others, and the copy number variations (CNVs) of FGF3, TERT, and SOX2 were found to be more frequent in our cohort than in cBioPortal datasets, and they were highly enriched in pathways in cancer and participated in complex biological regulatory processes. The TP53 mutation was the key mutation (76.9%, 30/39), and the most common amino acid alteration and mutation types were p.R249S (23.5%) and missense mutation (82.3%) in the TP53 variation. Furthermore, TP53 had more co-mutations with MUC17, NBPF10, and AHNAK2. However, there were no significant differences in clinical characteristics between HCC patients with mutant TP53 and wild-type TP53, and the overall survival rate between treatment via precision medication guided by NGS and that via empirical medication (logrank p = 0.181). Therefore, the role of NGS in the guidance of personalized targeted therapy, solely based on NGS, may be limited. Multi-center, large sample, prospective studies are needed to further verify these results.
Highlights
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide
We explored the correlations between high-frequency mutated genes and clinical characteristics of patients, and compared the efficacy between precision medication guided by next-generation sequencing (NGS) and empirical medication
By targeted panel and whole-exome sequencing, we identified 3,999 somatic variations among 86.4% (3,456/3,999) single nucleotide variants (SNVs), 11.9% (474/ 3,999) insertions/deletion variants (INDELs), and 1.7% (69/3,999) copy number variations (CNVs) in 39 hepatocellular carcinoma (HCC) patients
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Recent next-generation sequencing (NGS)-based studies have uncovered the genetic landscape of HCC (Totoki et al, 2014; Schulze et al, 2015; Cancer Genome Atlas Research, 2017), including driver mutations in TP53, CTNNB1, TERT promoter, and other key gene loci. The main purpose of NGS is to find the main driver gene in patients with advanced cancer and carry out targeted therapy, as well as to try to discover the molecular mutation target of drug resistance (Deng et al, 2019). There are still many unknown pathogenic variants waiting to be discovered. Identification of these alterations in cancer patients is the first step toward providing therapeutic targets
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