Analysis of genetic mutation characteristics in 40 Chinese patients with hepatocellular carcinoma.

[BACKGROUND] Hepatocellular carcinoma (HCC) is notable for its marked molecular heterogeneity and poor response to systemic therapy. Targeted next-generation sequencing (NGS) has facilitated the profiling of somatic alterations in HCC. However, the interpretation of panel-based genomic features such as tumor mutational burden (TMB), copy number alterations, and candidate gene fusions remains challenging, particularly in HBV-endemic Asian populations.

[OBJECTIVE] To explore the somatic mutation landscape of HCC using a targeted sequencing panel in a regional cohort and to descriptively assess its associations with clinicopathological characteristics.

[METHODS] We conducted a 671-gene targeted NGS panel covering approximately 2.5 Mb of coding regions on tumor-normal paired samples from 40 patients with HCC and integrated the mutational profiles with clinicopathological data. We analyzed somatic mutations, copy number variation signals, and candidate fusion events. We performed functional enrichment analyses and comparative analyses with the Cancer Genome Atlas (TCGA) cohort. Survival analyses were conducted in an exploratory manner.

[RESULTS] TP53 was the most frequently mutated gene (55%) and its mutation status was associated with hepatitis B virus infection, higher Edmondson-Steiner grade, and microvascular invasion. Panel-derived TMB values were evaluated descriptively, and exploratory survival analyses suggested potential differences between patient subgroups. Two candidate in-frame fusion signals, KIT-PDGFRA and ROS1-FBXL17, were detected in individual samples based on targeted DNA sequencing. Functional enrichment analyses indicated that mutated genes were mainly associated with cancer-related biological processes.

[CONCLUSIONS] This study provides an exploratory overview of somatic alterations detected by a targeted sequencing panel in a regional HCC cohort. Given the limitations inherent to panel-based analyses and the lack of independent validation, these findings should be interpreted cautiously and primarily serve as a reference for future large-scale and experimentally validated studies aimed at refining precision oncology strategies in HCC.