Solid Pseudopapillary Neoplasm (SPN)

Overview

Solid pseudopapillary neoplasm (SPN) is a rare low-malignant-potential pancreatic tumor occurring predominantly in young women. SPNs are characterized histologically by pseudopapillary architecture with solid and cystic regions, and they have a favorable prognosis with surgical resection. They are genetically distinct from other pancreatic cystic neoplasms, harboring near-universal CTNNB1 (beta-catenin) mutations and remarkably few other somatic alterations.

Cohorts in the corpus

  • pact_jhu_2011: 8 SPN cases sequenced by WES with matched normal tissue.

Recurrent alterations

  • Whole-exome sequencing of 8 SPNs revealed activating CTNNB1 mutations in all 8 (100%), targeting codons 32, 33, 34, or 37 of the beta-catenin phosphodegron; SPNs had only 2.9 +/- 2.1 nonsynonymous somatic mutations per tumor, the fewest of any tumor type evaluated by genome-wide sequencing at the time PMID:22158988.

Subtypes

  • No well-established molecular subtypes; the near-universal CTNNB1 mutation is the single defining driver.

Therapeutic landscape

  • CTNNB1/Wnt pathway activation is the primary oncogenic driver; no approved targeted therapies exist for SPN specifically, but the molecular profile may be informative for Wnt-pathway inhibitor trials.
  • The five-gene diagnostic panel (VHL, RNF43, CTNNB1, GNAS, KRAS) identifies SPNs by exclusive CTNNB1 mutation without mutations in the other four genes PMID:22158988.

Sources

  • PMID:22158988 — WES of 8 SPN cases defining somatic mutation landscape.

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