Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations

Radka Stoyanova, Margie L. Clapper, Alfonso Bellacosa, Elizabeth P. Henske, Joseph R. Testa, Eric A. Ross, Anthony T. Yeung, Emmanuelle Nicolas, Nicolaos Tsichlis, Yue Sheng Li, W. Marston Linehan, Sharon Howard, Kerry S. Campbell, Andrew K. Godwin, Bruce M. Boman, James A. Crowell, Levy Kopelovich, Alfred G. Knudson

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: The inherently complex signaling networks of tumors result from genetic and epigenetic alterations that occur during cancer initiation and progression. Methods: In an attempt to identify early molecular changes associated with dominantly inherited predisposition to "two-hit" renal tumors, the expression profiles of primary cultures of phenotypically normal renal epithelial cells from individuals bearing a germline mutation in either the von Hippel-Lindau (VHL) or the tuberous sclerosis complex (TSC) gene were compared to that of renal epithelial cells from control nonmutation carriers by microarray analysis. Results: Reliability of the microarray data from pooled samples was confirmed by real-time RT-PCR. Principal Component Analysis revealed substantial differences in the gene expression profiles of the renal epithelial cells from VHL and TSC mutation carriers. In several instances, the microarray data confirm our present knowledge of the cellular pathways affected by biallelic VHL and ISC mutations. Conclusions: These findings demonstrate that heterozygosity for a mutant tumor suppressor gene may alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner. Detectable effects of "one-hit" represent early molecular changes in tumorigenesis that may serve as targets for chemopreventive intervention.

Original languageEnglish (US)
Pages (from-to)1313-1321
Number of pages9
JournalCancer Biology and Therapy
Volume3
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

Keywords

  • Gene expression profiling
  • Microarrays
  • Renal cancer
  • Tuberous sclerosis
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Stoyanova, R., Clapper, M. L., Bellacosa, A., Henske, E. P., Testa, J. R., Ross, E. A., Yeung, A. T., Nicolas, E., Tsichlis, N., Li, Y. S., Linehan, W. M., Howard, S., Campbell, K. S., Godwin, A. K., Boman, B. M., Crowell, J. A., Kopelovich, L., & Knudson, A. G. (2004). Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations. Cancer Biology and Therapy, 3(12), 1313-1321. https://doi.org/10.4161/cbt.3.12.1459