Abstract
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.
Highlights
Solid pseudopapillary neoplasms (SPNs) are rare pancreatic tumors of unknown etiology, accounting for ~ 1% of all pancreatic exocrine neoplasms
Solid pseudopapillary neoplasms are characterized by the presence of somatic CTNNB1 exon 3 hotspot mutations
A Pan-Cancer analysis of 10 100 nonhypermutated cancers across 31 common cancer types from The Cancer Genome Atlas (TCGA) (Bailey et al, 2018; Gao et al, 2013) revealed that while CTNNB1 exon 3 mutations were present at 15–20% of liver, uterine, and adrenocortical carcinomas, mutations affecting CTNNB1 exon 3 are rare in other cancer types (< 3%; Fig. 1B)
Summary
Solid pseudopapillary neoplasms (SPNs) are rare pancreatic tumors of unknown etiology, accounting for ~ 1% of all pancreatic exocrine neoplasms. SPNs typically present as large, solitary, well-circumscribed lesions with indolent clinical course and a low propensity to metastasize (Klimstra et al, 2000; Ren et al, 2014). They are commonly managed surgically, some SPNs can exhibit a more aggressive behavior and metastasize. Solid pseudopapillary neoplasms are characterized by the presence of somatic CTNNB1 exon 3 hotspot mutations
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