Identification of tropomyosin kinase receptor (TRK) mutations in cancer.

1553 Background: TRK A, B and C, (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. Chromosomal rearrangements resulting in kinase fusions have been described across the NTRK gene family, and may contribute to tumorigenesis in diverse clinical settings. We searched for potentially activating mutations in the NTRK gene family by applying biologically driven ranking criteria to an anonymized next-generation sequencing dataset, sourced from Foundation Medicine (FMI) and Compendia BioSciences (Compendia). Methods: Approximately 10,000 patient samples were analyzed for mutations in NTRK1, NTRK2 or NTRK3. Mutation data in other known cancer-related genes were also captured for these tumors. Data were reconciled data across the disparate sources by mapping mutations to the canonical transcript for each gene where possible, or to a representative non-canonical transcript when the mutation occurred in a region not contai...