dc.contributor.author
Simon, Tincy
dc.contributor.author
Riemer, Pamela
dc.contributor.author
Jarosch, Armin
dc.contributor.author
Detjen, Katharina
dc.contributor.author
Domenico, Annunziata Di
dc.contributor.author
Bormann, Felix
dc.contributor.author
Menne, Andrea
dc.contributor.author
Khouja, Slim
dc.contributor.author
Monjé, Nanna
dc.contributor.author
Childs, Liam H.
dc.contributor.author
Lenze, Dido
dc.contributor.author
Leser, Ulf
dc.contributor.author
Rossner, Florian
dc.contributor.author
Morkel, Markus
dc.contributor.author
Blüthgen, Nils
dc.contributor.author
Pavel, Marianne
dc.contributor.author
Horst, David
dc.contributor.author
Capper, David
dc.contributor.author
Marinoni, Ilaria
dc.contributor.author
Perren, Aurel
dc.contributor.author
Mamlouk, Soulafa
dc.contributor.author
Sers, Christine
dc.date.accessioned
2023-12-13T13:23:51Z
dc.date.available
2023-12-13T13:23:51Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/41859
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-41580
dc.description.abstract
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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Cell-of-origin
en
dc.subject
Pancreatic neuroendocrine neoplasm
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
DNA methylation reveals distinct cells of origin for pancreatic neuroendocrine carcinomas and pancreatic neuroendocrine tumors
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
24
dcterms.bibliographicCitation.doi
10.1186/s13073-022-01018-w
dcterms.bibliographicCitation.journaltitle
Genome Medicine
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.volume
14
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
35227293
dcterms.isPartOf.eissn
1756-994X