下一代测序（NGS）研究表明，共同发生的散发性子宫内膜腺癌和卵巢癌（EEC/EOC）是克隆相关的，表明它们起源于单个原发肿瘤。尽管具有克隆性，但在早期诊断的同时发生的EEC/EOC表现出类似于孤立的原发EEC或孤立的原发EOC的低度恶性行为。本研究比较了共同发生的EEC/EOC与孤立的原发EEC和孤立的原发EOC的DNA甲基化特征。我们还进行了有针对性的NGS，以评估7个共同发生的EEC/EOC（基于病理学标准，其中4个为同步发生的EEC/EOC，3个为转移性EEC）。NGS证实了所有共同发生的EEC/EOC之间的克隆关系。DNA甲基化分型显示单独的原发EEC和单独的原发EOC具有不同的表观遗传标记。共同发生的EEC/EOC的子宫内膜肿瘤与孤立的原发EEC聚类，而它们的卵巢对应物与孤立的原发EOC聚类。具有腹膜病变的三个共同发生的EEC/EOC病例显示腹膜病变与EOC之间的表观遗传标记和拷贝数变异模式相比与EEC更接近。总之，同步散发性EEC/EOC是克隆相关的，但在卵巢和子宫肿瘤之间表观遗传标记发生变化，并且卵巢和腹膜肿瘤之间具有表观遗传的重叠。我们的结果表明，卵巢的肿瘤微环境可能在转移性EEC的表观遗传调控中发挥作用。版权所有 © 2023 Elsevier Inc.发布。

Next-generation sequencing (NGS) studies have demonstrated that co-occurring sporadic endometrioid endometrial and ovarian carcinomas (EEC/EOC) are clonally related, suggesting that they originate from a single primary tumor. Despite clonality, synchronous EEC/EOC when diagnosed at early stage behave indolently, similar to isolated primary EEC or isolated primary EOC. In the present study, we compared the DNA methylation signatures of co-occurring EEC/EOC to isolated primary EEC and isolated primary EOC. We also performed targeted NGS to assess the clonal relatedness of 7 co-occurring EEC/EOC (4 synchronous EEC/EOC and 3 metastatic EEC based on pathologic criteria). NGS confirmed a clonal relationship in all co-occurring EEC/EOC. DNA methylation profiling showed distinct epigenetic signatures of isolated primary EEC and isolated primary EOC. Endometrial tumors from co-occurring EEC/EOC clustered with the isolated primary EEC, while their ovarian counterparts clustered with isolated primary EOC. Three co-occurring EEC/EOC cases with peritoneal lesions showed a closer epigenetic signature and copy number variation profile between the peritoneal lesion and EOC than EEC. In conclusion, synchronous sporadic EEC/EOC are clonally related, but demonstrate a shift in DNA methylation signatures between ovarian and endometrial tumors as well as epigenetic overlap between ovarian and peritoneal tumors. Our results suggest that the tumor microenvironment in the ovary may play a role in epigenetic modulation of metastatic EEC.Copyright © 2023. Published by Elsevier Inc.