Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3-10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas. In the past decade, targeted gene and exome sequencing have uncovered additional pathogenic aberrations in each histotype. Moreover, an integrated genomic analysis by The Cancer Genome Atlas (TCGA) resulted in the molecular classification of endometrioid and serous carcinomas into four distinct subgroups, POLE (ultramutated), microsatellite instability (hypermutated), copy number low (endometrioid), and copy number high (serous-like). In this review, we provide an overview of the major molecular features of the aforementioned histopathological subtypes and TCGA subgroups and discuss potential prognostic and therapeutic implications for endometrial carcinoma.

中文翻译：

---

子宫内膜癌的分子遗传学。

子宫内膜癌是美国最常见的妇科恶性肿瘤。子宫内膜样子宫内膜癌约占新诊断病例的85％。浆液性癌约占诊断的3-10％；透明细胞癌占诊断的<5％；子宫癌和子宫肉瘤是罕见的双相性肿瘤。长期的分子观察表明，PTEN失活是子宫内膜样癌的主要驱动因素。TP53失活是大多数浆液性癌，某些高度子宫内膜样癌和许多子宫癌肉瘤的主要驱动因素；以及任何一个基因的失活都是某些透明细胞癌的驱动因素。在过去的十年中，靶向基因和外显子组测序发现了每种组织类型中的其他致病畸变。而且，癌症基因组图谱（TCGA）进行的综合基因组分析将子宫内膜样癌和浆液性癌的分子分类分为四个不同的亚组：POLE（超突变），微卫星不稳定性（超突变），拷贝数低（子宫内膜样）和拷贝数高（浆液状）。在这篇综述中，我们概述了上述组织病理学亚型和TCGA亚组的主要分子特征，并讨论了子宫内膜癌的潜在预后和治疗意义。