Identification of Targetable Rearrangements in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase () gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with -rearranged tumors. However, translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0.16%) that harbored an fusion gene: an exon 6 -exon 20 translocation (n=3), an exon 13 exon 20 translocation (n=1), and an exon 3 -exon 20 translocation (n=1). Among the most prevalent PDAC-related genes, activating mutations were absent in all 5 cases, who were <50 years of age. Among patients aged <50 years in our study cohort, translocations constituted 1.3% of PDACs. Four of 5 patients were treated with an ALK inhibitor, and 3 of these patients demonstrated stable disease, radiographic response, and/or normalization of serum CA 19-9. Although rare, fusions occur in PDAC, and screening for rearrangements should be considered in young patients with PDAC.