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Bellacosa A , Godwin AK , Peri S , Devarajan K , Caretti E , Vanderveer L , Bove B , Slater C , Zhou Y , Daly M , Howard S , Campbell KS , Nicolas E , Yeung AT , Clapper ML , Crowell JA , Lynch HT , Ross E , Kopelovich L , Knudson AG
Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations
Cancer Prev Res (Phila Pa). 2010 Jan;3(1) :48-61
PMID: 20051372    PMCID: PMC2804937   
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We hypothesized that cells bearing a single inherited "hit" in a tumor suppressor gene express an altered mRNA repertoire that may identify targets for measures that could delay or even prevent progression to carcinoma. We report here on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation carriers and controls. Our comparison analyses identified multiple changes in gene expression, in both tissues for both mutations, which were validated independently by real-time reverse transcription-PCR analysis. Several of the differentially expressed genes had been previously proposed as cancer markers, including mammaglobin in breast cancer and serum amyloid in ovarian cancer. These findings show that heterozygosity for a mutant tumor suppressor gene can alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner; these detectable effects of "one hit" represent early molecular changes in tumorigenesis that may serve as novel biomarkers of cancer risk and as targets for chemoprevention.
Bellacosa, Alfonso Godwin, Andrew K Peri, Suraj Devarajan, Karthik Caretti, Elena Vanderveer, Lisa Bove, Betsy Slater, Carolyn Zhou, Yan Daly, Mary Howard, Sharon Campbell, Kerry S Nicolas, Emmanuelle Yeung, Anthony T Clapper, Margie L Crowell, James A Lynch, Henry T Ross, Eric Kopelovich, Levy Knudson, Alfred G N01 CN-95037/CN/NCI NIH HHS/United States N01-CN-43309/CN/NCI NIH HHS/United States P30 CA06927/CA/NCI NIH HHS/United States P50 CA083638/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Cancer prevention research (Philadelphia, Pa.) Cancer Prev Res (Phila Pa). 2010 Jan;3(1):48-61.