Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations

Alfonso Bellacosa, Andrew K. Godwin, Suraj Peri, Karthik Devarajan, Elena Caretti, Lisa Vanderveer, Betsy Bove, Carolyn Slater, Yan Zhou, Mary Daly, Sharon Howard, Kerry S. Campbell, Emmanuelle Nicolas, Anthony T. Yeung, Margie L. Clapper, James A. Crowell, Henry T. Lynch, Eric Ross, Levy Kopelovich, Alfred G. Knudson

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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 genespecific 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.

Original languageEnglish (US)
Pages (from-to)48-61
Number of pages14
JournalCancer Prevention Research
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2010

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Bellacosa, A., Godwin, A. K., Peri, S., Devarajan, K., Caretti, E., Vanderveer, L., Bove, B., Slater, C., Zhou, Y., Daly, M., Howard, S., Campbell, K. S., Nicolas, E., Yeung, A. T., Clapper, M. L., Crowell, J. A., Lynch, H. T., Ross, E., Kopelovich, L., & Knudson, A. G. (2010). Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations. Cancer Prevention Research, 3(1), 48-61. https://doi.org/10.1158/1940-6207.CAPR-09-0078