Simon, Tincy; Riemer, Pamela; Jarosch, Armin; Detjen, Katharina; Di Domenico, Annunziata; Bormann, Felix; Menne, Andrea; Khouja, Slim; Monjé, Nanna; Childs, Liam H; Lenze, Dido; Leser, Ulf; Rossner, Florian; Morkel, Markus; Blüthgen, Nils; Pavel, Marianne; Horst, David; Capper, David; Marinoni, Ilaria; Perren, Aurel; ... (2022). DNA methylation reveals distinct cells of origin for pancreatic neuroendocrine carcinomas and pancreatic neuroendocrine tumors. Genome medicine, 14(1), p. 24. BioMed Central 10.1186/s13073-022-01018-w
|
Text
s13073-022-01018-w.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (9MB) | Preview |
BACKGROUND
Pancreatic neuroendocrine neoplasms (PanNENs) fall into two subclasses: the well-differentiated, low- to high-grade pancreatic neuroendocrine tumors (PanNETs), and the poorly-differentiated, high-grade pancreatic neuroendocrine carcinomas (PanNECs). While recent studies suggest an endocrine descent of PanNETs, the origin of PanNECs remains unknown.
METHODS
We performed DNA methylation analysis for 57 PanNEN samples and found that distinct methylation profiles separated PanNENs into two major groups, clearly distinguishing high-grade PanNECs from other PanNETs including high-grade NETG3. DNA alterations and immunohistochemistry of cell-type markers PDX1, ARX, and SOX9 were utilized to further characterize PanNECs and their cell of origin in the pancreas.
RESULTS
Phylo-epigenetic and cell-type signature features derived from alpha, beta, acinar, and ductal adult cells suggest an exocrine cell of origin for PanNECs, thus separating them in cell lineage from other PanNENs of endocrine origin.
CONCLUSIONS
Our study provides a robust and clinically applicable method to clearly distinguish PanNECs from G3 PanNETs, improving patient stratification.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Di Domenico, Annunziata, Marinoni, Ilaria, Perren, Aurel |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1756-994X |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
03 Mar 2022 11:04 |
Last Modified: |
05 Dec 2022 16:12 |
Publisher DOI: |
10.1186/s13073-022-01018-w |
PubMed ID: |
35227293 |
Uncontrolled Keywords: |
Cell-of-origin Epigenetics Pancreatic neuroendocrine neoplasm |
BORIS DOI: |
10.48350/166337 |
URI: |
https://boris.unibe.ch/id/eprint/166337 |
Actions (login required)
 |
Edit item |