Open AccessSolid pseudopapillary neoplasms of the pancreas are dependent on the Wnt pathway
Author(s) -
Selenica Pier,
Raj Nitya,
Kumar Rahul,
Brown David N.,
Arqués Oriol,
Reidy Diane,
Klimstra David,
Snuderl Matija,
Serrano Jonathan,
Palmer Héctor G.,
Weigelt Britta,
ReisFilho Jorge S.,
Scaltriti Maurizio
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12490
Subject(s) - pancreas , wnt signaling pathway , medicine , general surgery , cancer research , biology , microbiology and biotechnology , signal transduction
Solid pseudopapillary neoplasms (SPNs) are rare and relatively indolent tumors of the pancreas. While primary SPN s can be surgically resected, there are currently no therapies available for patients with advanced stage disease. Given that these tumors frequently carry CTNNB 1 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 SPN s were analyzed. We found that SPN s are characterized by a low‐complexity genome where somatic mutations in CTNNB 1 , 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), SPN s 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 SPN s to inhibitors of the Wnt pathway are warranted.