Abstract：
Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin and histogenesis currently remain unknown. Here, we investigated whole genome DNA methylation patterns and copy number variations (CNVs) in a series of MLAs in the context of a large cohort of various gynaecological carcinoma types. CNV analysis of 19 MLAs uncovered gains of chromosomes 1q (18/19, 95%), 10 (15/19, 79%), 12 (14/19, 74%), and 2 (10/19, 53%), as well as loss of chromosome 1p (7/19, 37%). Gains of chromosomes 1q, 10, and 12 were also identified in the majority of mesonephric adenocarcinomas of the uterine cervix (MAs) as well as subsets of endometrioid carcinomas (ECs) and low-grade serous carcinomas of the ovary (LGSCs) but only in a minority of serous carcinomas of the uterine corpus (USCs), clear cell carcinomas (CCCs), and tubo-ovarian high-grade serous carcinomas (HGSCs). While losses of chromosome 1p together with gains of chromosome 1q were also identified in both MA and LGSC, gains of chromosome 2 were almost exclusively identified in MLA and MA. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a co-clustering for MLAs and MAs, which was distinct from clusters of ECs, USCs, CCCs, LGSCs, and HGSCs. Group-wise comparisons confirmed a close epigenetic relationship between MLA and MA. These findings, in conjunction with the established histological and immunophenotypical overlap, suggest bona fide mesonephric differentiation, and support a more precise terminology of mesonephric-type adenocarcinoma instead of MLA in these tumours. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
摘要：
女性生殖道的中肾样腺癌（MLA）是一种罕见的组织型，可出现在子宫内膜和卵巢中。确切的细胞起源和组织发生目前尚不清楚。这里,我们研究了一系列MLA中的全基因组DNA甲基化模式和拷贝数变异(CNV),并纳入了大量不同类型的妇科肿瘤.19个MLA的CNV分析揭示了1q染色体的增益（18/19，95％），10（15/19，79%），12（14/19，74%），和2（10/19，53%），以及染色体1p的丢失（7/19，37％）。1q染色体的增益，在大多数子宫颈中肾腺癌（MAs）以及子宫内膜样癌（ECs）和卵巢低度浆液性癌（LGSCs）的亚群中也发现了10和12，但仅在少数子宫浆液性癌（USCs）中，透明细胞癌（CCCs），和输卵管卵巢高级别浆液性癌（HGSC）。虽然在MA和LGSC中也发现了染色体1p的丢失和染色体1q的增加，2号染色体的增益几乎只在MLA和MA中鉴定。DNA甲基化数据的无监督分层聚类和t-SNE分析（IlluminaEPIC阵列）确定了MLA和MA的共聚类，这与ECs集群不同，USC,CCCs,LGSCs,和HGSC。分组比较证实了MLA和MA之间的紧密表观遗传关系。这些发现,结合已建立的组织学和免疫表型重叠，表明真正的中肾分化，并支持更精确的中肾型腺癌术语，而不是这些肿瘤中的MLA。©2023作者。由JohnWiley＆SonsLtd代表英国和爱尔兰病理学会出版的病理学杂志。
