{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T08:31:52Z","timestamp":1769243512814,"version":"3.49.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"DOI":"10.3389\/fonc.2019.00517","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T12:34:17Z","timestamp":1560947657000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Wwox Deletion in Mouse B Cells Leads to Genomic Instability, Neoplastic Transformation, and Monoclonal Gammopathies"],"prefix":"10.3389","volume":"9","author":[{"given":"Kevin M.","family":"McBride","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunsuk","family":"Kil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxiang","family":"Mu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua B.","family":"Plummer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej J.","family":"Zelazowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manu","family":"Sebastian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin C.","family":"Abba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Marcelo","family":"Aldaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,19]]},"reference":[{"key":"B1","first-page":"2140","article-title":"WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3\u201324.1, a region frequently affected in breast cancer","volume":"60","author":"Bednarek","year":"2000","journal-title":"Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1093\/hmg\/9.11.1651","article-title":"Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells","volume":"9","author":"Ried","year":"2000","journal-title":"Hum Mol Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1002\/gcc.10047","article-title":"The common fragile site FRA16D and its associated gene WWOX are highly conserved in the mouse at Fra8E1","volume":"34","author":"Krummel","year":"2002","journal-title":"Genes Chromosomes Cancer"},{"key":"B4","first-page":"8068","article-title":"WWOX, the FRA16D gene, behaves as a suppressor of tumor growth","volume":"61","author":"Bednarek","year":"2001","journal-title":"Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1038\/nature08768","article-title":"Signatures of mutation and selection in the cancer genome","volume":"463","author":"Bignell","year":"2010","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.bbcan.2014.06.001","article-title":"WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies","volume":"1846","author":"Aldaz","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3949","DOI":"10.1073\/pnas.0609783104","article-title":"Targeted deletion of Wwox reveals a tumor suppressor function","volume":"104","author":"Aqeilan","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e7775","DOI":"10.1371\/journal.pone.0007775","article-title":"Generation and characterization of mice carrying a conditional allele of the Wwox tumor suppressor gene","volume":"4","author":"Ludes-Meyers","year":"2009","journal-title":"PLoS ONE"},{"key":"B10","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/s41419-018-0896-z","article-title":"Somatic loss of WWOX is associated with TP53 perturbation in basal-like breast cancer","volume":"9","author":"Abdeen","year":"2018","journal-title":"Cell Death Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/gcc.20497","article-title":"WWOX hypomorphic mice display a higher incidence of B-cell lymphomas and develop testicular atrophy","volume":"46","author":"Ludes-Meyers","year":"2007","journal-title":"Genes Chromosomes Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1182\/blood-2010-12-323659","article-title":"Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines","volume":"118","author":"Roy","year":"2011","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1093\/hmg\/ddw112","article-title":"Identification of a novel susceptibility locus at 16q23.1 associated with childhood acute lymphoblastic leukemia in Han Chinese","volume":"25","author":"Shi","year":"2016","journal-title":"Hum Mol Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1097\/QAI.0b013e3181d3d9eb","article-title":"Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas: an integrated analysis of DNA copy number and gene expression","volume":"54","author":"Deffenbacher","year":"2010","journal-title":"J Acquir Immune Defic Syndr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1365-2141.2009.07943.x","article-title":"Genome wide DNA-profiling of HIV-related B-cell lymphomas","volume":"148","author":"Capello","year":"2010","journal-title":"Br J Haematol"},{"key":"B16","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1182\/blood.V91.12.4457","article-title":"Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma","volume":"91","author":"Chesi","year":"1998","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1182\/blood-2012-12-471888","article-title":"Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells","volume":"121","author":"Walker","year":"2013","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3291","DOI":"10.1182\/blood-2007-02-075069","article-title":"Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma","volume":"110","author":"Jenner","year":"2007","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1038\/leu.2009.174","article-title":"International Myeloma Working Group molecular classification of multiple myeloma: spotlight review","volume":"23","author":"Fonseca","year":"2009","journal-title":"Leukemia"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.1182\/blood-2016-01-631200","article-title":"Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group","volume":"127","author":"Sonneveld","year":"2016","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1002\/gcc.20668","article-title":"A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect","volume":"48","author":"Agnelli","year":"2009","journal-title":"Genes Chromosomes Cancer"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1158\/1078-0432.CCR-09-2831","article-title":"Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcome","volume":"16","author":"Dickens","year":"2010","journal-title":"Clin Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1182\/blood-2018-08-870022","article-title":"Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma","volume":"132","author":"Walker","year":"2018","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41375-018-0196-8","article-title":"A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis","volume":"33","author":"Walker","year":"2019","journal-title":"Leukemia"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4372","DOI":"10.3892\/ol.2017.6672","article-title":"Recurrent alterations of the WW domain containing oxidoreductase gene spanning the common fragile site FRA16D in multiple myeloma and monoclonal gammopathy of undetermined significance","volume":"14","author":"Handa","year":"2017","journal-title":"Oncol Lett"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5580","DOI":"10.1038\/sj.onc.1204640","article-title":"Mechanisms of chromosomal translocations in B cell lymphomas","volume":"20","author":"Kuppers","year":"2001","journal-title":"Oncogene"},{"key":"B27","doi-asserted-by":"publisher","first-page":"17046","DOI":"10.1038\/nrdp.2017.47","article-title":"Multiple myeloma","volume":"3","author":"Kumar","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B28","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cell.2013.01.007","article-title":"Mechanisms of programmed DNA lesions and genomic instability in the immune system","volume":"152","author":"Alt","year":"2013","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2010.03.016","article-title":"Origin of chromosomal translocations in lymphoid cancer","volume":"141","author":"Nussenzweig","year":"2010","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nature10909","article-title":"DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes","volume":"484","author":"Hakim","year":"2012","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nsmb.1773","article-title":"Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation","volume":"17","author":"Simsek","year":"2010","journal-title":"Nat Struct Mol Biol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1093\/nar\/25.6.1317","article-title":"B lymphocyte-specific, Cre-mediated mutagenesis in mice","volume":"25","author":"Rickert","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1002\/gene.20025","article-title":"A keratin K5Cre transgenic line appropriate for tissue-specific or generalized Cre-mediated recombination","volume":"39","author":"Ramirez","year":"2004","journal-title":"Genesis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1093\/brain\/awt338","article-title":"The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation","volume":"137","author":"Mallaret","year":"2014","journal-title":"Brain"},{"key":"B35","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1182\/blood.V100.1.246","article-title":"Bethesda proposals for classification of lymphoid neoplasms in mice","volume":"100","author":"Morse","year":"2002","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1158\/0008-5472.CAN-06-1561","article-title":"Anaplastic, plasmablastic, and plasmacytic plasmacytomas of mice: relationships to human plasma cell neoplasms and late-stage differentiation of normal B cells","volume":"67","author":"Qi","year":"2007","journal-title":"Cancer Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"8798","DOI":"10.1073\/pnas.0603272103","article-title":"Regulation of hypermutation by activation-induced cytidine deaminase phosphorylation","volume":"103","author":"McBride","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B38","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/nature06020","article-title":"IgH class switching and translocations use a robust non-classical end-joining pathway","volume":"449","author":"Yan","year":"2007","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1084\/jem.20040052","article-title":"Deletion of the nucleotide excision repair gene Ercc1 reduces immunoglobulin class switching and alters mutations near switch recombination junctions","volume":"200","author":"Schrader","year":"2004","journal-title":"J Exp Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.1084\/jem.20170468","article-title":"Phosphorylation promotes activation-induced cytidine deaminase activity at the Myc oncogene","volume":"214","author":"Mu","year":"2017","journal-title":"J Exp Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.1084\/jem.20081319","article-title":"Regulation of class switch recombination and somatic mutation by AID phosphorylation","volume":"205","author":"McBride","year":"2008","journal-title":"J Exp Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1038\/sj.onc.1201409","article-title":"Deletional remodeling of c-myc-deregulating chromosomal translocations","volume":"15","author":"Kovalchuk","year":"1997","journal-title":"Oncogene"},{"key":"B43","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.cell.2004.08.006","article-title":"AID is required for c-myc\/IgH chromosome translocations in vivo","volume":"118","author":"Ramiro","year":"2004","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/S1074-7613(03)00262-0","article-title":"The Smu tandem repeat region is critical for Ig isotype switching in the absence of Msh2","volume":"19","author":"Min","year":"2003","journal-title":"Immunity"},{"key":"B45","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1098\/rstb.2008.0196","article-title":"Non-homologous end joining in class switch recombination: the beginning of the end","volume":"364","author":"Kotnis","year":"2009","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/B978-0-12-380995-7.00003-3","article-title":"Mapping of switch recombination junctions, a tool for studying DNA repair pathways during immunoglobulin class switching","volume":"108","author":"Stavnezer","year":"2010","journal-title":"Adv Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-0-12-394300-2.00001-6","article-title":"Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks","volume":"116","author":"Boboila","year":"2012","journal-title":"Adv Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e1004654","DOI":"10.1371\/journal.pgen.1004654","article-title":"Mechanism of suppression of chromosomal instability by DNA polymerase POLQ","volume":"10","author":"Yousefzadeh","year":"2014","journal-title":"PLoS genetics"},{"key":"B49","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1084\/jem.20092449","article-title":"Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4","volume":"207","author":"Boboila","year":"2010","journal-title":"J Exp Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s12026-009-8142-5","article-title":"Controlling somatic hypermutation in immunoglobulin variable and switch regions","volume":"47","author":"Maul","year":"2010","journal-title":"Immunol Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.cell.2011.07.049","article-title":"Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells","volume":"147","author":"Chiarle","year":"2011","journal-title":"Cell"},{"key":"B52","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.cell.2011.07.048","article-title":"Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes","volume":"147","author":"Klein","year":"2011","journal-title":"Cell"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.cell.2008.09.062","article-title":"AID is required for the chromosomal breaks in c-myc that lead to c-myc\/IgH translocations","volume":"135","author":"Robbiani","year":"2008","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.molcel.2014.01.011","article-title":"Arginine methylation facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation","volume":"53","author":"Yang","year":"2014","journal-title":"Mol Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.mrfmmm.2017.07.002","article-title":"Microhomology-mediated end joining: Good, bad and ugly","volume":"809","author":"Seol","year":"2017","journal-title":"Mutat Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/nrc3537","article-title":"End-joining, translocations and cancer","volume":"13","author":"Bunting","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1182\/blood-2011-08-376236","article-title":"Dendritic cell-mediated activation-induced cytidine deaminase (AID)-dependent induction of genomic instability in human myeloma","volume":"119","author":"Koduru","year":"2012","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","first-page":"6997","DOI":"10.1038\/ncomms7997","article-title":"APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma","volume":"6","author":"Walker","year":"2015","journal-title":"Nat Commun"},{"key":"B59","doi-asserted-by":"publisher","first-page":"E4716","DOI":"10.1073\/pnas.1409252111","article-title":"WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response","volume":"111","author":"Abu-Odeh","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1038\/onc.2016.389","article-title":"Wwox-Brca1 interaction: role in DNA repair pathway choice","volume":"36","author":"Schrock","year":"2017","journal-title":"Oncogene"},{"key":"B61","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1002\/gcc.22693","article-title":"WWOX, the FRA16D gene: A target of and a contributor to genomic instability","volume":"58","author":"Hussain","year":"2019","journal-title":"Genes Chromosomes Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2019.00517\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T15:53:13Z","timestamp":1575042793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2019.00517\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,19]]},"references-count":61,"alternative-id":["10.3389\/fonc.2019.00517"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2019.00517","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,19]]},"article-number":"517"}}