title: Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations.
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 TSC 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.
authors.affiliation: Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Radka
authors.initials: R
authors.lastname: Stoyanova
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bellacosa
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Henske
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
authors.forename: Eric A
authors.initials: EA
authors.lastname: Ross
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Yeung
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nicolas
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Tsichlis
authors.forename: Yue-Sheng
authors.initials: YS
authors.lastname: Li
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Sharon
authors.initials: S
authors.lastname: Howard
authors.forename: Kerry S
authors.initials: KS
authors.lastname: Campbell
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Boman
authors.forename: James A
authors.initials: JA
authors.lastname: Crowell
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.forename: Alfred G
authors.initials: AG
authors.lastname: Knudson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C486009:TESC protein, human; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human