Yao Yu

Genomic Characterization of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features in Black Individuals

Abstract Black individuals experience worse survival after a diagnosis of high-grade serous ovarian carcinoma (HGSC) than White individuals and are underrepresented in ovarian cancer research. To date, the understanding of the molecular and genomic heterogeneity of HGSC is based primarily on the evaluation of tumors from White individuals. In the present study, we performed whole-exome sequencing on HGSC samples from 211 Black patients to identify significantly mutated genes and characterize mutational signatures, assessing their distributions by gene expression subtypes. The occurrence and frequency of somatic mutations and signatures by self-reported race were compared with historic data from The Cancer Genome Atlas (TCGA). Despite technical differences (e.g., formalin-fixed vs. fresh-frozen tissue), the distribution of mutations and their variant classifications for major HGSC genes were nearly identical across study populations. However, de novo significantly mutated gene analysis identified genes not previously reported in TCGA analysis, including the oncogene KRAS and the potential tumor suppressor OBSCN. The prevalence of the homologous recombination deficiency signature was higher among Black individuals with the immunoreactive gene expression subtype compared with the mesenchymal and proliferative subtypes. These findings were confirmed by comparing the data from Black patients with those from 123 White patients with identical tissue collection and processing. Overall, this study suggests that, although most features of HGSC tumor phenotypes are similar in Black and White populations, there may be clinically relevant differences. If validated, these phenotypes may be important for clinical decision-making and would have been missed by characterizing tumors from White individuals only. Significance: Elucidation of the somatic mutational landscape of high-grade serous ovarian carcinoma in Black individuals, who experience poor survival and are underrepresented in research, could inform patient prognosis and enable precision medicine opportunities.