Rare copy number variants observed in hereditary breast cancer cases disrupt genes in estrogen signaling and TP53 tumor suppression network

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dc.contributor.author Pylkäs, Katri
dc.contributor.author Vuorela, Mikko
dc.contributor.author Otsukka, Meeri
dc.contributor.author Kallioniemi, Anne
dc.contributor.author Jukkola-Vuorinen, Arja
dc.contributor.author Wingvist, Robert
dc.date.accessioned 2012-09-06T07:23:07Z
dc.date.available 2012-09-06T07:23:07Z
dc.date.issued 2012
dc.identifier.issn 1553-7390 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66328
dc.description Public Library of Science open access -
dc.description.abstract Abstract Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number variants (CNVs) in breast cancer predisposition, high-resolution genome-wide scans were performed on genomic DNA of 103 BRCA1, BRCA2, and PALB2 mutation negative familial breast cancer cases and 128 geographically matched healthy female controls; for replication an independent cohort of 75 similarly mutation negative young breast cancer patients was used. All observed rare variants were confirmed by independent methods. The studied breast cancer cases showed a consistent increase in the frequency of rare CNVs when compared to controls. Furthermore, the biological networks of the disrupted genes differed between the two groups. In familial cases the observed mutations disrupted genes, which were significantly overrepresented in cellular functions related to maintenance of genomic integrity, including DNA double-strand break repair (P = 0.0211). Biological network analysis in the two independent breast cancer cohorts showed that the disrupted genes were closely related to estrogen signaling and TP53 centered tumor suppressor network. These results suggest that rare CNVs represent an alternative source of genetic variation influencing hereditary risk for breast cancer. -
dc.language.iso en -
dc.title Rare copy number variants observed in hereditary breast cancer cases disrupt genes in estrogen signaling and TP53 tumor suppression network -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal Article| -
dc.identifier.urn URN:NBN:fi:uta-201209061032 -
dc.identifier.doi doi:10.1371/journal.pgen.1002734 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Biokemia, solu- ja molekyylibiologia | en=Biochemistry, cell and molecular biology| -
dc.administrativeunit fi=Biolääketieteellisen teknologian yksikkö | en=Institute of Biomedical Technology| -
dc.journal.title Plos Genetics -
dc.journal.volume 8 -
dc.journal.number 6 -
dc.journal.volumepagerange 1-9 -
dc.journal.url http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002734 -

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