Journal Article

DKFZ-2025-01297

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mucinous cystic neoplasms of the pancreas and liver share a similar DNA methylation profile with mucinous ovarian tumors.

Leoni, Z. ; Calina, T. G. ; Janik, T.DKFZ* ; Grafenhorst, E. ; Taube, E. T. ; Neumann, C. C. ; Chen, B. ; Braicu, E. I. ; Sehouli, J. ; Malinka, T. ; Schöning, W. ; Pratschke, J. ; Calin, G. A. ; Klimstra, D. S. ; Benhamida, J. K. ; Esposito, I. ; Möbs, M. ; Horst, D.DKFZ* ; Schallenberg, S. ; Capper, D.DKFZ* ; Dragomir, M.-P.DKFZ*

2025
Wiley Bognor Regis [u.a.]

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Please use a persistent id in citations: doi:10.1002/path.6439

Abstract: The origin of mucinous cystic neoplasms (MCNs) remains a major challenge in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian-like stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and six hepatic MCNs (MCN-L). Using immunohistochemistry and targeted DNA sequencing, we unequivocally established the diagnosis of MCN. Unsupervised DNA methylation profile analysis of reference classes of pancreatic neoplasms (11 entities and normal pancreatic tissue from 224 unique samples) revealed that MCN-P predominantly forms a distinct group. In the DNA methylation landscape of liver tumors, encompassing five tumor types and normal bile duct tissue from 136 unique samples, MCN-L demonstrated a specific methylation profile when compared with all other entities. Furthermore, within the DNA methylation landscape of ovarian tumors - featuring five tumor types, normal Fallopian tube, and normal ovarian tissue from 90 unique samples - we found that both MCN-P and MCN-L grouped with mucinous ovarian carcinoma and mucinous borderline ovarian tumors (mBOTs). Notably, low-grade MCNs exhibited greater DNA methylation similarities to mBOTs, while high-grade or invasive MCNs were primarily associated with mucinous ovarian carcinomas. When analyzing all samples together (19 tumor types and four normal tissue types, n = 430), MCNs similarly grouped with mucinous ovarian tumors and normal ovarian tissue. Additionally, in a network analysis of differentially methylated probes, MCN-P and MCN-L share significant methylation traits, closely resembling mucinous ovarian tumors. In conclusion, our findings highlight that MCN-P and MCN-L are distinct entities in the landscape of pancreatic and hepatic tumors and show DNA methylation profile similarities with mucinous ovarian tumors, suggesting a potential common origin. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keyword(s): DNA methylation ; mucinous borderline ovarian tumor ; mucinous cystic neoplasms ; mucinous ovarian carcinoma

Note: 2025 Sep;267(1):10-24

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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