Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target.

ABSTRACT: The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib. This work demonstr

SUBMITTER: Cook PJ 

PROVIDER: S-EPMC5508201 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature