Targeted next generation sequencing of pancreatic solid pseudopapillary neoplasms show mutations in Wnt signaling pathway genes.

Abstract

Solid pseudopapillary neoplasms of the pancreas are rare neoplasms that have been shown to harbor recurrent somatic pathogenic variants in the beta-catenin gene, CTNNB1. Here, we used targeted next generation sequencing to analyze these tumors for other associated mutations. Six cases of solid pseudopapillary neoplasms were studied. DNA extracted from formalin-fixed paraffin embedded tissue blocks was analyzed using the Ion Torrent platform, with the 50-gene Ampliseq Cancer Hotspot Panel v2 (CHPv2), with further variant validation performed by Sanger sequencing. Four tumors (67%) were confirmed to harbor mutations within CTNNB1, two with c.109T > G p.(Ser37Ala) and two with c.94G > A p.(Asp32Asn). One case showed a frameshift deletion in the Adenomatous Polyposis Coli gene, APC c.3964delG p.(Glu1322Lysfs*93) with a variant allele frequency of 42.6%. Sanger sequencing on non-tumoral tissue confirmed the variant was somatic. The patient with the APC mutation developed metastasis and died. In addition to the four cases harboring CTNNB1 variants, we found a case characterized by poor outcome, showing a rare frameshift deletion in the APC gene. Since the APC product interacts with beta-catenin, APC variants may, in addition to CTNNB1, contribute to the pathogenesis of solid pseudopapillary neoplasms via the Wnt signaling pathway.