欧洲和美国最常见的妇科恶性肿瘤是子宫内膜癌。与大多数癌症一样，早期子宫内膜癌预后较好，而高级别的内膜型和非内膜型癌症预后最差。在内膜型人类肿瘤中，肿瘤抑制基因PTEN和p53（Trp53）经常发生变异或丧失，根据The Cancer Genome Atlas的数据鉴定。这些抑制基因体细胞突变或基因表达丧失可能导致肿瘤的发展、进展和治疗抵抗。此外，F-box和WD重复结构蛋白7（FBXW7）这种另一个肿瘤抑制基因也常见体细胞错义突变。FBXW7是SCF-βTrCP泛素连接酶复合体的一部分，负责信号蛋白的降解。具体而言，FBXW7负责结合和促进参与增殖和迁移的蛋白质的不稳定性。失去多个肿瘤抑制基因的功能可能会激活与恶性肿瘤进展、恶性度、治疗抵抗和不同肿瘤亚型形成相关的途径。本期EMBO Mol Med中Brown等人的研究为恶性子宫内膜癌中肿瘤抑制基因突变的复杂性提供了深入了解。 © 2023 The Author. 根据CC BY 4.0 许可协议发布。

The most common gynecological cancer in Europe and the United States is endometrial. Like most cancers, early-stage endometrial cancer has a more favorable prognosis, while high-grade, including endometrioid and nonendometrioid, has the worst prognosis. In endometrioid human tumors, the tumor suppressor genes PTEN and p53 (Trp53) are frequently altered or lost, as identified in datasets from The Cancer Genome Atlas. These suppressors' somatic mutations or loss of gene expression can lead to neoplastic development, tumor progression, and therapeutic resistance. In addition, somatic missense mutations are prevalent in another tumor suppressor, the F-box and WD repeats containing 7 (FBXW7). FBXW7 is part of the SCF-βTrCP ubiquitin complex that signals protein destruction. Specifically, FBXW7 is responsible for binding and facilitating the destabilization of proteins involved in proliferation and migration. Losing the function of multiple tumor suppressors could activate pathways involved in neoplastic progression, malignancy, therapeutic resistance, and formation of different tumor subtypes. The study by Brown et al in this issue of EMBO Mol Med (Brown et al, 2023) provides insight into the complexity of tumor suppressor mutations in malignant endometrial cancer.© 2023 The Author. Published under the terms of the CC BY 4.0 license.