Abstract C052: Endometrial cancer genomics varies by race

Abstract Introduction Variability in endometrial cancer (EC) risk and outcomes exist, with Black women disproportionately negatively affected related to White women. The biologic etiologies of these observations are poorly understood. Our objective was to describe the somatic mutations of the tumor genome and compare them to RNA expression in self-identified Black and White women diagnosed with EC. Methods Women with newly diagnosed EC and undergoing hysterectomy were recruited prospectively. Fresh tumors obtained at the time of surgery were flash-frozen, underwent DNA and RNA extraction and were submitted for whole exome sequencing (WES) analysis (DNA) or bulk RNA sequencing analysis. Differentially expressed genes between racial groups and tumor grade were calculated using Deseq2. Genomic ancestry was determined using ADMIXTURE. Chi-square and Mann Whitney U tests were used for analyses, with a threshold for significance of p<0.05. Results A total of 49 patients with EC were included. Thirty (61.2%) women were diagnosed with low-grade EC and 19 (38.8%) with high grade EC. Twenty (40.8%) women self-identified as Black, 27 (55.1%) as White and 2 (4.1%) as Asian/other. Admixture analysis showed that 36 (73.4%) had >14% African ancestry. The remaining 13 (26.5%) patients had admixed European and Native American ancestry, with <1% African ancestry. In the RNA-seq, we found significant DEGs by tumor grade; with 2132 DEG in High grade compared to Low grade tumors with a false discovery rate of <0.05 and a fold change (FC) of ≤-1.5 or ≥1.5. Top 10 DEG included MT4, TAF15, SLFN5 and PLEKHS1 (upregulated) and MCRIP1, MAZ, MYOM3, PRPH, BCL7C, AC016700.5 (downregulated). In the WES analysis, 8 Black women had mutations in GON4L compared to 1 in the White woman (44.4% vs 3.7%, padj=0.04); and 7 Black women had a mutation in PRAMEF14 compared to 1 White woman (38.8% vs 3.7%, padj= 0.06). Conclusion GON4L, which is a transcription factor associated with decreased apoptosis and promotion of tumor growth through CD24 regulation, was significantly more mutated in the EC genome of Black women relative to White women. Somatic mutation and transcriptional changes are seen between tumor grade and self-identified race and require further exploration for its relationship to aggressive disease. Citation Format: Alex P. Sanchez-Covarrubias, Ramlogan Sowamber, Leah Dodds, Andre Pinto, Sophia George, Matthew Schlumbrecht. Endometrial cancer genomics varies by race [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C052.