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

Chromosomal rearrangements, including translocations, require formation and joining of DNA double strand breaks (DSBs). These events disrupt the integrity of the genome and are frequently involved in producing leukemias, lymphomas and sarcomas. Despite the importance of these events, current understanding of their genesis is limited. To examine the origins of chromosomal rearrangements we developed Translocation Capture Sequencing (TC-Seq), a method to document chromosomal rearrangements genome-wide, in primary cells. We examined over 180,000 rearrangements obtained from 400 million B lymphocytes, revealing that proximity between DSBs, transcriptional activity and chromosome territories are key determinants of genome rearrangement. Specifically, rearrangements tend to occur in cis and to transcribed genes. Finally, we find that activation-induced cytidine deaminase (AID) induces the rearrangement of many genes found as translocation partners in mature B cell lymphoma.Copyright © 2011 Elsevier Inc. All rights reserved. PMID: 21962510 Funding information This work was supported by: NIGMS NIH HHS, United States Grant ID: T32 GM007739 NIAID NIH HHS, United States Grant ID: R37 AI037526 NIAID NIH HHS, United States Grant ID: AI037526 Howard Hughes Medical Institute, United States NIAID NIH HHS, United States Grant ID: R01 AI037526-17 Intramural NIH HHS, United States NIGMS NIH HHS, United States Grant ID: GM07739 NIAID NIH HHS, United States Grant ID: R01 AI037526 More Less keyboard_arrow_down