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

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.

Tumor tissue from Black and White patients with serous or endometrioid ECs underwent DNA sequencing using the UNCseq^TM 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.

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 (vs. 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 ARID1A or PTEN (p < 0.05).

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.