Mesonephric-like adenocarcinoma harbours characteristic copy number variations and a distinct DNA methylation signature closely related to mesonephric adenocarcinoma of the cervix

• Verfasst von: Kommoss, Felix [VerfasserIn]
• Verfasst von: Lee, Cheng-Han [VerfasserIn]
• Verfasst von: Tessier-Cloutier, Basile [VerfasserIn]
• Verfasst von: Gilks, C Blake [VerfasserIn]
• Verfasst von: Stewart, Colin JR [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Köbel, Martin [VerfasserIn]
• Titel: Mesonephric-like adenocarcinoma harbours characteristic copy number variations and a distinct DNA methylation signature closely related to mesonephric adenocarcinoma of the cervix
• Verf.angabe: Felix KF Kommoss, Cheng-Han Lee, Basile Tessier-Cloutier, C Blake Gilks, Colin JR Stewart, Andreas von Deimling and Martin Köbel
• E-Jahr: 2024
• Jahr: January 2024
• Umfang: 6 S.
• Illustrationen: Illustrationen
• Fussnoten: Online veröffentlicht: 18. Oktober 2023 ; Gesehen am 19.01.2024
• Titel Quelle: Enthalten in: The journal of pathology
• Ort Quelle: Bognor Regis [u.a.] : Wiley, 1892
• Jahr Quelle: 2024
• Band/Heft Quelle: 262(2024), Seite 4-9
• ISSN Quelle: 1096-9896
• DOI: doi:10.1002/path.6217
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: clear cell
• Sach-SW: copy number variations
• Sach-SW: DNA methylation
• Sach-SW: endometrial cancer
• Sach-SW: endometrioid
• Sach-SW: gynaecological tract
• Sach-SW: mesonephric
• Sach-SW: mesonephric-like
• Sach-SW: ovarian cancer
• Sach-SW: serous
• K10plus-PPN: 1878502689

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.