Comprehensive Molecular Characterization of High-Grade Endometrial Cancer in an Ancestrally-Diverse Cohort

Frimer, Marina, Gee, Devin, Goldstein, Zoe R, Hooper, WillIam F, Founta, Kyriaki, Deschenes, Astrid, Geiger, Heather, Belleau, Pascal, Kramer, Melissa, Yueh, Brian, Chu, Tim, Oku, Ali, Vaksman, Zalman, Grether, Valentina, Steinsnyder, Zoe, Araneo, Andrew L, Chung, Charlie, Kapedani, Arisa, Nizam, Aaron, Eskiocak, Onur, Ozler, Kadir, Goldberg, Gary L, Krasnitz, Alexander, McCombie, WR, Barbi, Mali, Winterkorn, Lara, Robine, Nicolas, Beyaz, Semir, Chambwe, Nyasha (May 2026) Comprehensive Molecular Characterization of High-Grade Endometrial Cancer in an Ancestrally-Diverse Cohort. bioRxiv. ISSN 2692-8205 (Submitted)

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Abstract

Endometrial cancer (EC) exhibits one of the most striking racial disparities in oncology with black women disproportionately affected by aggressive high-grade subtypes that have poorer outcomes. While social and environmental factors undoubtedly contribute, the molecular underpinnings of these disparities remain critically understudied. To bridge this knowledge gap, we performed matched tumor-normal whole-genome sequencing and tumor transcriptome sequencing on 71 predominantly high-grade EC patient samples from an ancestrally diverse cohort of women recruited at a large hospital system in the New York metropolitan area. Our analysis characterized the germline and somatic mutation landscape, identifying ancestry-associated molecular differences. Notably, focal amplification of the EVI1 transcription factor (encoded at the MECOM locus) was significantly more frequent in African ancestry patients and associated with poorer clinical outcomes in an external validation cohort. Additionally transcriptome analysis revealed decreased CD8+ T cell infiltration with increasing African ancestry, suggesting tumor immune microenvironment differences with potential therapeutic implications.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types > endometrial cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Beyaz lab
CSHL labs > Krasnitz lab
CSHL labs > McCombie lab
CSHL labs > Tuveson lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 5 May 2026
Date Deposited: 26 May 2026 12:21
Last Modified: 26 May 2026 12:21
PMCID: PMC13174477
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42213

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