Next-generation sequencing demonstrates racial and sex differences in genomic profiling of hepatocellular carcinoma patients: an AACR GENIE project analysis

Background: Genomic variations related to racial and sex differences among patients with hepatocellular carcinoma (HCC) have not been investigated. We sought to characterize the mutational landscape of patients with HCC relative to race and sex. Methods: The American Association for Cancer Research GENIE project (v16.0) was used to assess data on genomic variations among adult patients (>18 years) with HCC who underwent next-generation sequencing. Variations in 787 genes were identified and characterized relative to race and sex. Results: Among 832 patients, 60.8 % of individuals were White, 7.7 % Black, and 12.4 % Asian (other/ unknown:19.1 %). Most patients had genetic data from the primary tumor (71.2 %), whereas 17.2 % had metastatic disease sequenced (unknown:11.6 %). TERT mutations occurred more frequently in White (48.0 %) and Black (46.7 %) versus Asian (23.4 %) patients (q = 0.003), while TP53 mutations were more common in Asian (48.6 %) versus Black (45.5 %) or White (33.1 %) individuals (q = 0.03). TERT (46.1 % vs. 28.6 %) and CTNNB1 mutations (47.7 % vs. 29.3 %) were more likely to occur in males than females (both q < 0.05). Marked variations in prevalence of other common genetic HCC mutations were noted across different races and sexes. Conclusions: Differences in mutational profiles of HCC patients highlight the importance of accruing diverse populations of patients to clinical trials.