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dc.contributor.authorWang, Jing
dc.contributor.authorAlt, Frederick W.
dc.contributor.authorGostissa, Monica
dc.contributor.authorDatta, Abhishek
dc.contributor.authorMurphy, Michael C.
dc.contributor.authorAlimzhanov, Marat B.
dc.contributor.authorCoakley, Kristen M.
dc.contributor.authorRajewsky, Klaus
dc.contributor.authorManis, John P.
dc.contributor.authorYan, Catherine T.
dc.date.accessioned2011-04-18T03:06:11Z
dc.date.issued2008
dc.identifier.citationWang, Jing H., Frederick W. Alt, Monica Gostissa, Abhishek Datta, Michael Murphy, Marat B. Alimzhanov, Kristen M. Coakley, Klaus Rajewsky, John P. Manis, and Catherine T. Yan. 2008. Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. The Journal of Experimental Medicine 205(13): 3079-3090.en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4853410
dc.description.abstractNonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch recombination (CSR) in peripheral B lymphocytes. We now show that CD21-cre–mediated deletion of the Xrcc4 NHEJ gene in p53-deficient peripheral B cells leads to recurrent surface Ig-negative B lymphomas (“CXP lymphomas”). Remarkably, CXP lymphomas arise from peripheral B cells that had attempted both receptor editing (secondary V[D]J recombination of Igκ and Igλ light chain genes) and IgH CSR subsequent to Xrcc4 deletion. Correspondingly, CXP tumors frequently harbored a CSR-based reciprocal chromosomal translocation that fused IgH to c-myc, as well as large chromosomal deletions or translocations involving Igκ or Igλ, with the latter fusing Igλ to oncogenes or to IgH. Our findings reveal peripheral B cells that have undergone both editing and CSR and show them to be common progenitors of CXP tumors. Our studies also reveal developmental stage-specific mechanisms of c-myc activation via IgH locus translocations. Thus, Xrcc4/p53-deficient pro–B lymphomas routinely activate c-myc by gene amplification, whereas Xrcc4/p53-deficient peripheral B cell lymphomas routinely ectopically activate a single c-myc copy.en_US
dc.language.isoen_USen_US
dc.publisherThe Rockefeller University Pressen_US
dc.relation.isversionofdoi:10.1084/jem.20082271en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605230/pdf/en_US
dash.licenseLAA
dc.titleOncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switchingen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe Journal of Experimental Medicineen_US
dash.depositing.authorRajewsky, Klaus
dc.date.available2011-04-18T03:06:11Z
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dc.identifier.doi10.1084/jem.20082271*
dash.contributor.affiliatedMurphy, Michael
dash.contributor.affiliatedGostissa, Monica
dash.contributor.affiliatedDatta, Abhishek
dash.contributor.affiliatedWang, Jing
dash.contributor.affiliatedYan, Catherine
dash.contributor.affiliatedManis, John
dash.contributor.affiliatedAlt, Frederick
dash.contributor.affiliatedRajewsky, Klaus


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