Newton Meredith A, Merker Jason D, Gong Weida, Patil Sushant, Tan Xianming, Cocoran David L, Pfefferle Adam D, Hayward Michele C, Broaddus Russell, Nichols Hazel B, Olshan Andrew F, Weissman Bernard, Keku Temitope O, Bae-Jump Victoria
University of North Carolina at Chapel Hill, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, United States.
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, United States.
Gynecol Oncol Rep. 2025 Jun 25;60:101795. doi: 10.1016/j.gore.2025.101795. eCollection 2025 Aug.
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 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 (. 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).
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.
利用一项机构资助的靶向测序研究，描述黑人和白人患者子宫内膜样癌和浆液性子宫内膜癌（EC）的基因组差异，并研究其对临床结局的影响。
使用UNCseq检测板对黑人和白人浆液性或子宫内膜样EC患者的肿瘤组织进行DNA测序。利用病历中的临床病理数据，评估所有患者以及组织学和分子亚类患者的无进展生存期（PFS）和总生存期（OS）。
纳入了200例子宫内膜样或浆液性EC的肿瘤组织，其中169例（84.5%）来自白人患者，31例（15.5%）来自黑人患者。与白人患者相比，黑人患者的浆液性肿瘤（.子宫内膜样肿瘤，p<0.0001）和TP53突变肿瘤（根据改良的TCGA亚分类，p=0.01）更为常见。在中位随访62.4个月期间，黑人患者的PFS和OS显著缩短（p<0.04）。改良的TCGA分类中，TP53突变肿瘤的PFS和OS最差（p<0.04）。浆液性肿瘤中，25.0%被分类为POLE、微卫星高度不稳定（MSI）或TP53野生型，而11.6%的子宫内膜样肿瘤被分类为TP53突变型。白人患者的或体细胞突变更为常见（p<0.05）。
确定了EC种族差异的几个潜在分子驱动因素。未来有必要开展研究，在更多样化的研究人群中验证这些发现的临床影响，并评估其作为治疗中临床可操作靶点的潜力。
