Transcription-coupled genetic instability marks acute lymphoblastic leukemia structural variation hotspots.

ABSTRACT: Progression of malignancy to overt disease requires multiple genetic hits. Activation-induced deaminase (AID) can drive lymphomagenesis by generating off-target DNA breaks at loci that harbor highly active enhancers and display convergent transcription. The first active transcriptional profiles from acute lymphoblastic leukemia (ALL) patients acquired here reveal striking similarity at structural variation (SV) sites. Specific transcriptional features, namely convergent transcription and Pol2 stalling, were detected at breakpoints. The overlap was most prominent at SV with recognition motifs for the recombination activating genes (RAG). We present signal feature analysis to detect vulnerable regions and quantified from human cells how convergent transcription contributes to R-loop generati

SUBMITTER: Heinaniemi M 

PROVIDER: S-EPMC4951197 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature