Molecular genetic changes in solid pseudopapillary neoplasms (SPN) of the pancreas.

Abstract

749 Background: Solid Pseudopapillary Neoplasms (SPNs) of the pancreas are rare accounting for 1-2% of all pancreatic tumors. Previous studies had shown that a pathogenic mutation of the CTNNB1 gene is present in over 90% of the SPN tumors with very limited information available on the specific molecular changes present in SPN. Here we report the results of next generation genetic testing of a large series of SPN tumors from the Foundation Medicine database. Methods: Foundation Medicine database from 07/2012 to 04/2019 was reviewed. A total of 31 cases of SPN tumors were identified out of 12,892 cases of pancreatic cancers. Information collected included demographic information on the patients as well as tumor analysis for next generation genetic sequencing of 315 genes associated with cancer with FoundationOne or 324 genes associated with FoundationOneCDx. Microsatellite stability status and tumor mutation burden were determined. Results: Twenty nine out of 31 cases (93%) had a CTNNB1 mutation. Seventy percent of the CTNNB1 mutations were on position 32 (14 cases, 41%) or in position 37 (9 cases, 29%). Other sites of CTNNB1 mutations included position 34 (3 cases, 9.6%), position 2 (2 cases, 6.4%) and position 38 (1 case, 3.2%). Two cases did not have a CTNNB1 mutation, one had a CDKN2A mutation and the other had no detectable mutations. Most cases had additional mutations aside from the CTNNB1, the most common were TP53 (3 cases, 9.6%) and LRP1B (2 cases, 6.4%). Other accompanying mutations were seen just once. Twenty-five percent of these cases had actionable gene mutations, each found in one case including: MSH2, BRCA2, ATM, XRCC3, ATRX, PTEN, ESR1, CDKN2, and PIK3CA. Conclusions: Next generation genetic testing of SPN tumors is of clinical benefit since it identifies actionable mutations in 29% of the cases.