Comprehensive genomic profiling to identify recurrent kinase fusions in pancreatic ductal adenocarcinoma.

Abstract

292 Background: Kinases activated by gene fusions represent an important class of oncogenes that have been detected in hematologic and solid malignancies. These fusion genes have been well-described in non-small cell lung cancer, and such patients often benefit from matched kinase inhibitors. Recent work in pancreatic ductal adenocarcinoma (PDAC) has also identified recurrent ALK and BRAF rearrangements. Further, patients harboring the former have benefited from ALK inhibitors, as previously reported. We present a survey of kinase fusion genes identified in a large, consecutive series of PDACs. Methods: In the context of clinical care, hybrid-capture based CGP was performed prospectively on 3,426 PDACs for up to 315 cancer-related genes and intronic regions of up to 28 genes that are commonly rearranged in cancer. Results: Overall, kinase fusion genes were identified in 32 (1%) patients with PDAC. The patients consisted of 8 females and 23 males, and ranged in age between 31 and 83 years (median, 58 years). PDACs harboring kinase fusions were predominantly KRAS-wildtype (97%). In fact, the prevalence of kinase fusion genes among KRAS-wildtype PDACs was 8%. Gene fusions involved BRAF (n = 22), ALK (n = 5), NTRK (n = 3) and MET (n = 2). Concurrent genomic alterations included CDKN2A/B (41%), TP53 (28%), GNAS (19%), SMAD4 (16%), MCL1 (16%), ARID1A (13%) and MYC (13%). Updated clinical history will be presented on patients, who previously benefitted from ALK inhibitors. Conclusions: Recurrent gene fusions involving BRAF, ALK, NTRK and MET occur in a subset of PDACs. Although rare, these kinase fusions potentially represent actionable targets and screening should be considered, especially in KRAS-wildtype PDACs.