Emmet J Jordan, Olca Basturk, Steven D Leach, David S Klimstra, Peter J Allen, Michael F Berger, Gokce Askan, Christine A Iacobuzio-Donahue, Kenneth H Yu, Eileen M O’Reilly, Maeve A Lowery
Context Adenosquamous carcinoma of the pancreas represents a rare subtype (1-4%) of exocrine pancreatic cancer for which the clinical and molecular features are not well defined. Objective We reviewed clinical characteristics and performed comprehensive molecular profiling in a cohort of patients with adenosquamous carcinoma of the pancreas treated at MSKCC diagnosed from January 2000-July 2015 from a prospectively maintained database, following IRB approval to provide further insight into this disease. Design Samples were reviewed to optimally select the squamous component for molecular profiling using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay platform 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 were sequenced on an Illumina HiSeq 2500. Results Median overall survival for those with stage IV disease was 3.0 months (95%CI 0-13.5) and for those who underwent primary curative resection was 13.0 months (95%CI 7.5-18.5). Sixteen patients had sufficient tissue/consent for analysis. KRAS (100%), TP53 (75%) and SMAD4 (38%) alterations were most common while FAT1 (19%), JAK3 (19%), U2AF1 (6%) and PIK3R1 (6%) mutations occurred at lower frequencies. Copy number alterations such as amplification of Mcl-1(31%), MYC (6%) and FGFR1genes (6%) were detected. Conclusions Adenosquamous carcinoma of the pancreas like conventional ductal adenocarcinoma has a poor prognosis with a comparable molecular signature for the most common alterations with rarer novel alterations observed which can guide research in a disease with a need for therapeutic improvement.
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