Assessment of genomic alterations in adenosquamous carcinoma of the pancreas (ASCOP).

Abstract

261 Background: ASCOP represents a rare subtype (1-4%) of exocrine pancreatic cancer for which the clinical and molecular features are not well defined. We reviewed clinical characteristics and performed comprehensive molecular profiling in a cohort of patients with ASCOP treated at MSKCC. Methods: Patients (pts) with ASCOP diagnosed from January 2000-July 2015 were identified from a prospectively maintained database, following IRB approval. Clinicopathological data including time to progression (TTP), recurrence-free interval (RFI) and overall survival (OS) were recorded. Samples were reviewed by a pancreas pathologist to optimally select the squamous component for molecular profiling using MSK-IMPACT platform. This is a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of 410 key cancer genes. Tumor and matched normal libraries (where available; n=9) were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline to detect single nucleotide variants, short indels, copy number aberrations and structural rearrangements. Results: We identified 84 pts with ASCOP of whom 15 had sufficient tissue/consent for analysis. Median OS for resected pts was 17 months (mo) and 6 mo respectively. Median PFS on 1st line therapy (FLT) for stage IV disease was 3 mo. 53 pts underwent surgical resection, of whom 11 remain disease free at median follow up of 24 mo. 15/15 (100%) had KRAS mutations (mut). 11/15 (73%) had TP53 mut. 6/15 (40%) had SMAD4 mut [4 point mutations (PM), 2 frameshift deletions]. 6/15 (40%) had CDKN2A mut (4 deletions, 2 PM). Mut were also found in FAT 1 (3/15), JAK3 3 (3/15), TBX 3 (2/15) and FGFR amplification was found in 1 pt sample. Conclusions: ASCOP like conventional ductal adenocarcinoma has a poor prognosis with a comparable molecular signature in the most common alterations. Potential targets e.g., FGFR1 may allow novel agents in select pts. [Table: see text]