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dc.contributor.author공구-
dc.date.accessioned2019-11-22T00:59:07Z-
dc.date.available2019-11-22T00:59:07Z-
dc.date.issued2017-03-
dc.identifier.citationNATURE GENETICS, v. 49, no. 3, page. 341-348en_US
dc.identifier.issn1061-4036-
dc.identifier.issn1546-1718-
dc.identifier.urihttps://www.nature.com/articles/ng.3771-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/113390-
dc.description.abstractSomatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may be sites of selective susceptibility to double-strand-break damage due to high transcriptional activity or, through incrementally increasing copy number, may be sites of secondary selective pressure. The transcriptomic consequences ranged from strong individual oncogene effects to weak but quantifiable multigene expression effects. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences, from modest to strong effects, thereby supporting a polygenic model of cancer development.en_US
dc.description.sponsorshipData used in this analysis were funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (BASIS), a European research project funded by the European Community's Seventh Framework Programme (FP7/2010-2014) under grant agreement number 242006; the Triple Negative project, funded by the Wellcome Trust (grant reference 077012/Z/05/Z); and the HER2+ project, funded by Institut National du Cancer (INCa) in France (grant nos. 226-2009, 02-2011, 41-2012, 144-2008 and 06-2012). J.W.M.M. received funding for this project through an ERC Advanced grant (no. 322737). G.K. is supported by National Research Foundation of Korea grants (NRF 2015R1A2A1A10052578). The ICGC Asian Breast Cancer Project was funded through a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111218-SC01). D.G. is supported by the EU-FP7-SUPPRESSTEM project. S.N.-Z. is funded by a Wellcome Trust Intermediate Fellowship (WT100183MA) and is supported as a Wellcome Beit Fellow.en_US
dc.language.isoen_USen_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.subjectGENOME-WIDE ASSOCIATIONen_US
dc.subjectTERT PROMOTER MUTATIONSen_US
dc.subjectSIGNATURESen_US
dc.subjectLANDSCAPEen_US
dc.subjectLEUKEMIAen_US
dc.subjectTHERAPYen_US
dc.subjectOVARIANen_US
dc.subjectREPAIRen_US
dc.titleA somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancersen_US
dc.typeArticleen_US
dc.relation.no3-
dc.relation.volume49-
dc.identifier.doi10.1038/ng.3771-
dc.relation.page341-348-
dc.relation.journalNATURE GENETICS-
dc.contributor.googleauthorGlodzik, Dominik-
dc.contributor.googleauthorMorganella, Sandro-
dc.contributor.googleauthorDavies, Helen-
dc.contributor.googleauthorSimpson, Peter T.-
dc.contributor.googleauthorLi, Yilong-
dc.contributor.googleauthorZou, Xueqing-
dc.contributor.googleauthorDiez-Perez, Javier-
dc.contributor.googleauthorStaaf, Johan-
dc.contributor.googleauthorAlexandrov, Ludmil B.-
dc.contributor.googleauthorKong, Gu-
dc.relation.code2017002199-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF MEDICINE[S]-
dc.sector.departmentDEPARTMENT OF MEDICINE-
dc.identifier.pidgkong-
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