title: Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Klein
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Resch
authors.forename: Mila
authors.initials: M
authors.lastname: Jankovic
authors.forename: Thiago
authors.initials: T
authors.lastname: Oliveira
authors.forename: Arito
authors.initials: A
authors.lastname: Yamane
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nakahashi
authors.forename: Michela
authors.initials: M
authors.lastname: Di Virgilio
authors.forename: Anne
authors.initials: A
authors.lastname: Bothmer
authors.forename: Andre
authors.initials: A
authors.lastname: Nussenzweig
authors.forename: Davide F
authors.initials: DF
authors.lastname: Robbiani
authors.forename: Rafael
authors.initials: R
authors.lastname: Casellas
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000378:metabolism; D016259:Genes, myc; D016678:Genome; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D013154:Spleen / Q000166:cytology; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007143:Immunoglobulin Heavy Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase