Tumor Suppressor Genes

  • Tumor Suppressor Genes are the counterpart to oncogenes.
  • Inactivation of Tumor Suppressor Genes favours tumor growth.
  • Cancer phenotype is recessive.
    • However, If induced by viruses, cancer phenotype is dominant.
  • Tumor Suppressor Genes can explain the phenomenon of familial cancer syndroms.
  • Tumor Suppressor Genes may be inactivated by LOH (loss of heterozygosity / allelic deletion).
  • LOH occurs at a far higher frequency that mutational alterations. That is why the loss of a TSG is more frequent than somatic mutations (10^6 for one allele, 10^12 for both at the same time).
  • Tumor Suppressor Genes may be inactivated by disabling the promoter.
  • In order to “find” Tumor Suppressor Genes / “find” genes that are not there in the phenotype of interest (cancer), genetic markers that are close to the gene of interest can be used:
    • Restriction fragment length polymorphism: Depends first on SNPs that affect one allele but not the other and second on restriction enzymes that cleave this site.
    • PCR: Also depends on SNPs that affect one allele but not the other: However, in this case there are primers used that are specific to sequences that are polymorphic.
  • Tumor Suppressor Genes are either gatekeepers (direct cells through growth, division and death) or caretakers (maintenance of the genome, genomic stability).
  • Examples for Tumor Suppressor Genes:
    • RB: retinobastoma, osteosarcoma; transcriptional repession, control of E2Fs
    • APC: familial adenomatous polyposis coli; β-catenin degradation ( see also)
    • p53:
    • VHL: Von Hippel-Lindau disease; ubiquitin ligase
    • TGFBR2: TGF-β receptor
    • p16: familial melanoma; CDK inhibitor
    • p14: p53 stabilizer
    • NF1: neurofibromatosis type 1; Ras-GAP
    • NF2: neurofibroma-position syndrome; cytoskeleton-membrane linkage
    • PTEN: breast and gastrointestinal carcinomas; PIP3 phosphatase
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