Racial differences in endometrial cancer genomics and outcomes using UNCseq targeted DNA sequencing.

Objective: To use an institution-sponsored targeted sequencing effort to characterize the genomic differences in endometrioid and serous endometrial cancers (ECs) between Black and White patients and to investigate the impact on clinical outcomes.

Methods: Tumor tissue from Black and White patients with serous or endometrioid ECs underwent DNA sequencing using the UNCseq panel. Progression-free survival (PFS) and overall survival (OS) were assessed for all patients and within histologic and molecular subcategories using clinicopathologic data from the medical record.

Results: Tumor tissue from 200 endometrioid or serous ECs were included, with 169 tumors (84.5 %) from White and 31 (15.5 %) from Black patients. Black patients more frequently had serous (. endometrioid, p < 0.0001) and TP53 mutant (by modified TCGA subclassification, p = 0.01) tumors, compared to White patients. Over a median follow-up of 62.4 months, PFS and OS were significantly shorter for Black patients (p < 0.04). Modified TCGA categorized TP53 mutant tumors had the worst PFS and OS (p < 0.04). Of serous tumors, 25.0 % were categorized as POLE, MSI or TP53 wild type, whereas 11.6 % of endometrioid tumors were categorized as TP53 mutant. White patients more often had somatic mutations in or (p < 0.05).

Conclusions: Several potential molecular drivers of the racial disparity in EC were identified. Future studies are warranted to validate the clinical impact of these findings amongst a larger diverse study population and evaluate their potential as clinically actionable targets in treatment.