Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers.

ABSTRACT: Tyrosine kinase (TK) fusions are frequently found in cancers, either as initiating events or as a mechanism of resistance to targeted therapy. Partner genes and exons in most TK fusions are followed typical recurrent patterns, but the underlying mechanisms and clinical implications of these patterns are poorly understood. By developing Functionally Active Chromosomal Translocation Sequencing (FACTS), we discover that typical TK fusions involving ALK, ROS1, RET and NTRK1 are selected from pools of chromosomal rearrangements by two major determinants: active transcription of the fusion partner genes and protein stability. In contrast, atypical TK fusions that are rarely seen in patients showed reduced protein stability, decreased downstream oncogenic signaling, and were less responsive to in

SUBMITTER: Cheong TC 

PROVIDER: S-EPMC11178778 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature