Search: onr:"swepub:oai:DiVA.org:uu-523490" >
The Evolutionary Hi...
The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation.
-
Backman, Samuel (author)
-
Botling, Johan (author)
-
Nord, Helena (author)
-
show more...
-
Ghosal, Suman (author)
-
Stålberg, Peter (author)
-
- Juhlin, C Christofer (author)
- Karolinska Institutet
-
Almlöf, Jonas (author)
-
- Sundin, Anders (author)
- Uppsala universitet,Radiologi
-
Zhang, Liang (author)
-
Moens, Lotte (author)
-
Eriksson, Barbro (author)
-
Welin, Staffan (author)
-
Hellman, Per (author)
-
Skogseid, Britt (author)
-
Pacak, Karel (author)
-
Mollazadegan, Kazhan (author)
-
Åkerström, Tobias (author)
-
Crona, Joakim (author)
-
show less...
-
(creator_code:org_t)
- 2024
- 2024
- English.
-
In: medRxiv : the preprint server for health sciences.
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients. Following MEN1 inactivation, PanNETs exhibit genetic heterogeneity on both spatial and temporal dimensions with parallel and convergent tumuor evolution involving the ATRX/DAXX and mTOR pathways. Following alkylating chemotherapy treatment, some PanNETs develop mismatch repair deficiency and acquire a hypermutator phenotype. This DNA hypermutation phenotype was only found in cases that also showed transformation into a high-grade PanNET. Overall, our findings contribute to broaden the understanding of metastatic PanNET, and suggests that therapy driven disease evolution is an important hallmark of this disease.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Backman, Samuel
-
Botling, Johan
-
Nord, Helena
-
Ghosal, Suman
-
Stålberg, Peter
-
Juhlin, C Christ ...
-
show more...
-
Almlöf, Jonas
-
Sundin, Anders
-
Zhang, Liang
-
Moens, Lotte
-
Eriksson, Barbro
-
Welin, Staffan
-
Hellman, Per
-
Skogseid, Britt
-
Pacak, Karel
-
Mollazadegan, Ka ...
-
Åkerström, Tobia ...
-
Crona, Joakim
-
show less...
- Articles in the publication
- medRxiv : the pr ...
- By the university
-
Uppsala University
-
Karolinska Institutet