title: The expression of tumour suppressors and proto-oncogenes in tissues susceptible to their hereditary cancers.
abstract: BACKGROUND
  Studies of familial cancers have found that only a small subset of tissues are affected by inherited mutations in a given tumour suppressor gene (TSG) or proto-oncogene (POG), even though the mutation is present in all tissues. Previous tests have shown that tissue specificity is not due to the presence vs absence of gene expression, as TSGs and POGs are expressed in nearly every type of normal human tissue. Using published microarray expression data we tested the related hypothesis that tissue-specific expression of a TSG or POG is highest in tissue where it is of oncogenic importance.
  
  
  METHODS
  We tested this hypothesis by examining whether individual TSGs and POGs had higher expression in the normal (noncancerous) tissues where they are implicated in familial cancers relative to those tissues where they are not. We examined data for 15 TSGs and 8 POGs implicated in familial cancer across 12 human tissue types.
  
  
  RESULTS
  We found a significant difference between expression levels in susceptible vs nonsusceptible tissues. It was found that 9 (60%, P<0.001) of the TSGs and 5 (63%, P<0.001) of the POGs had their highest expression level in the tissue type susceptible to their oncogenic effect.
  
  
  CONCLUSIONS
  This highly significant association supports the hypothesis that mutation of a specific TSG or POG is likely to be most oncogenic in the tissue where the gene has its highest level of expression. This suggests that high expression in normal tissues is a potential marker for linking cancer-related genes with their susceptible tissues.
authors.affiliation: Department of Biology, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Muir
authors.affiliation: Department of Biology, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Nunney
mesh_terms: D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes