Abstract C085: The somatic genomic landscape of hepatocellular carcinoma by race and ethnicity
Authors: Maldonado J. Alberto , Greten Tim F. , Monge Cecilia 
Published: December 2023

Background: Hepatocellular carcinoma (HCC) has generally well-known causative agents; key genetic alterations are emerging form a heterogenous molecular landscape. Although the genomic landscape of hepatocellular carcinoma (HCC) has been well studied in recent years; however, previous genomic studies have disproportionately included non-Hispanic White (NHW) patients with limited inclusion of racial and ethnic minorities, particularly non-Hispanic Black (NHB) and Hispanic patients. We describe somatic mutation differences in a larger and more racially and ethnically representative HCC cohort than previously characterized. Methods: HCC mutational data was downloaded from The Cancer Genome Atlas (TCGA) project, an international data registry with 2.5 petabytes of genomic data, on cBioPortal. Non-Hispanic White, NHB and Hispanic (of any race), and Asian patients were analyzed. Median Fraction of Genes Altered (FGA) was calculated for all mutations. The primary objective was to compare the mutation frequencies between NHW and others with respect to fourteen genes of interest. Five genes (TERT, TP53, CTNNB1, AXIN1, ARID1A) are reported in literature as the most common HCC mutations, five other genes (ARID2, NFE2L2, KEAP1, RPS6KA3, JAK1) were identified as novel genes, and the remaining four (AJAP1, ADARB2, PTPRN2, SDK1) have been identified as part of potentially important  epigenetic processes. Fisher’s Exact Test with a False Discovery Rate correction was used to calculate the statistical significance of the differences in mutation frequency between NHW and other patient groups. Results: Patients in the HCC cohort included 1,136 individuals (NHW N= 418, 50.7%; NHB N= 34, 4.1%; Hispanic N= 35, 4.2%; Asian N= 338, 41.0%). When compared to the NHW group, NHB patients had higher rates of TP53 mutations (69.7% vs 23.6%, p &lt;0.00001, FDR &lt;0.00004) while Hispanic patients had more SDK1 mutations (22.9% vs 4.3%, p= 0.0005, FDR= 0.005). Asian patients had higher frequency of TERT (38.1% vs 13.1%, p= 0.0051, FDR= 0.017), TP53 (36.2% vs 23.6%, p= 0.0002, FDR= 0.003), AXIN1 (9.8% vs 3.9%%, p= 0.0016, FDR= 0.007), and JAK1 (5.3% vs 1.2%, p= 0.0012, FDR= 0.008) mutations. All other comparisons between groups did not reach statistical significance. Median FGA for all patients was 0.24 with Asian patients presenting with higher rates as compared to NHW patients (0.28 vs 0.21, p &lt;0.00001). Conclusions: The advances of cancer genomics has provided important insight into new therapeutics. Similarly, understanding the somatic genomic landscape of HCC in different patient populations is critical as we aim towards increased use of targeted therapies. In this study, TERT, TP53, AXIN1, JAK1, and SDK1 mutations were shown to occur at different frequencies in specific racial and ethnic groups. These differences in molecular landscape amongst racial and ethnic groups could contribute to precision medicine strategies used to address HCC.

Citation Format: J. Alberto Maldonado, Tim F. Greten, Cecilia Monge. The somatic genomic landscape of hepatocellular carcinoma by race and ethnicity [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C085.