PMID- 21962510 OWN - NLM STAT- MEDLINE DCOM- 20111130 LR - 20250103 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 147 IP - 1 DP - 2011 Sep 30 TI - Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. PG - 95-106 LID - 10.1016/j.cell.2011.07.048 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Klein, Isaac A AU - Klein IA AD - Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. FAU - Resch, Wolfgang AU - Resch W FAU - Jankovic, Mila AU - Jankovic M FAU - Oliveira, Thiago AU - Oliveira T FAU - Yamane, Arito AU - Yamane A FAU - Nakahashi, Hirotaka AU - Nakahashi H FAU - Di Virgilio, Michela AU - Di Virgilio M FAU - Bothmer, Anne AU - Bothmer A FAU - Nussenzweig, Andre AU - Nussenzweig A FAU - Robbiani, Davide F AU - Robbiani DF FAU - Casellas, Rafael AU - Casellas R FAU - Nussenzweig, Michel C AU - Nussenzweig MC LA - eng GR - R01 AI037526/AI/NIAID NIH HHS/United States GR - GM07739/GM/NIGMS NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - R01 AI037526-17/AI/NIAID NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States GR - T32 GM007739/GM/NIGMS NIH HHS/United States GR - AI037526/AI/NIAID NIH HHS/United States GR - R37 AI037526/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Immunoglobulin Heavy Chains) RN - EC 3.5.4.- (AICDA (Activation-Induced Cytidine Deaminase)) RN - EC 3.5.4.5 (Cytidine Deaminase) SB - IM CIN - Cell. 2011 Sep 30;147(1):20-2. doi: 10.1016/j.cell.2011.09.005. PMID: 21962501 CIN - Nat Rev Genet. 2011 Oct 18;12(11):741. doi: 10.1038/nrg3090. PMID: 22005978 MH - Animals MH - B-Lymphocytes/*metabolism MH - Cells, Cultured MH - Cytidine Deaminase/metabolism MH - Genes, myc MH - *Genome MH - Humans MH - Immunoglobulin Heavy Chains/genetics MH - Mice MH - *Mutagenesis MH - Neoplasms/genetics MH - Sequence Analysis, DNA/methods MH - Spleen/cytology MH - *Translocation, Genetic MH - AICDA (Activation-Induced Cytidine Deaminase) PMC - PMC3190307 MID - NIHMS322290 EDAT- 2011/10/04 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/09/30 CRDT- 2011/10/04 06:00 PHST- 2011/05/24 00:00 [received] PHST- 2011/07/14 00:00 [revised] PHST- 2011/07/27 00:00 [accepted] PHST- 2011/10/04 06:00 [entrez] PHST- 2011/10/04 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/09/30 00:00 [pmc-release] AID - S0092-8674(11)00999-8 [pii] AID - 10.1016/j.cell.2011.07.048 [doi] PST - ppublish SO - Cell. 2011 Sep 30;147(1):95-106. doi: 10.1016/j.cell.2011.07.048.