Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes.

摘要: Chromosomal rearrangements, including translocations, require formation and joining of DNA double strand breaks (DSBs). These events disrupt the integrity genome are frequently involved in producing leukemias, lymphomas sarcomas. Despite importance these events, current understanding their genesis is limited. To examine origins chromosomal rearrangements we developed Translocation Capture Sequencing (TC-Seq), a method to document genome-wide, primary cells. We examined over 180,000 obtained from 400 million B lymphocytes, revealing that proximity between DSBs, transcriptional activity chromosome territories key determinants rearrangement. Specifically, tend occur cis transcribed genes. Finally, find activation-induced cytidine deaminase (AID) induces rearrangement many genes found as translocation partners mature cell lymphoma.