association between acquired uniparental disomy and homozygous mutations and her2erpr status in breast cancer联系获得单亲的二体性和纯合突变和her2erpr状态在乳腺癌.pdf

Association between Acquired Uniparental Disomy and Homozygous Mutations and HER2/ER/PR Status in Breast Cancer 1 2 1 2 1 Musaffe Tuna *, Marcel Smid , Dakai Zhu , John W. M. Martens , Christopher I. Amos 1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 2 Department of Medical Oncology, Erasmus Medical Center Josephine Nefkens Institute and Cancer Genomics Center, Rotterdam, The Netherlands Abstract Background: Genetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing. Methods/Principal Findings: We retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. aUPD was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using pr