Solid pseudopapillary neoplasms of the pancreas are dependent on the Wnt pathway.
SPN
Wnt
beta-catenin
gene expression
methylation
pancreas
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
15
11
2018
revised:
07
02
2019
accepted:
08
04
2019
pubmed:
12
4
2019
medline:
6
5
2020
entrez:
12
4
2019
Statut:
ppublish
Résumé
Solid pseudopapillary neoplasms (SPNs) are rare and relatively indolent tumors of the pancreas. While primary SPNs can be surgically resected, there are currently no therapies available for patients with advanced stage disease. Given that these tumors frequently carry CTNNB1 hotspot (recurrently mutated loci in a gene) mutations resulting in β-catenin nuclear accumulation, it has been speculated that the Wnt pathway may be a driver in this disease. Here, we present a comprehensive "multi-omics" study where the genome, transcriptome, and methylome of SPNs were analyzed. We found that SPNs are characterized by a low-complexity genome where somatic mutations in CTNNB1, present in 100% of the cases, are the only actionable genomic lesions. Compared to more common subtypes of pancreatic tumors (adenocarcinomas and pancreatic neuroendocrine tumors), SPNs show high expression levels of genes belonging to the Wnt pathway. Their methylome was consistent with an epithelial cell origin and a general upregulation of Wnt pathway genes. Clinical studies to evaluate the exquisite sensitivity of SPNs to inhibitors of the Wnt pathway are warranted.
Identifiants
pubmed: 30972907
doi: 10.1002/1878-0261.12490
pmc: PMC6670010
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1684-1692Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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