What are tumor suppressor genes?
Genes needed for control of cell growth
Mechanisms of tumor suppressor gene inactivation (5)
- loss of heterozygosity
- mutation of allele : missense / STOP codon
- epigenetic
- transdominance
- haploinsufficiency
Epigenetic modification of tumor suppressor gene
hypermethylation of promoter silences transcription
What is transdominance?
1 gene is mutated, the other isn’t - mutated protein silences the “normal” protein
Tumor suppressor gene inactivation in hereditary cancers
One mutated allele is present in the family and the other one happens sporadically
Tumor suppressor gene inactivation in sporadic cancers
Requires two mutations to silence the gene on both alleles
WT1 gene function, hereditary neoplasm and sporadic neoplasm
- regulates nuclear transcription
- causes Wilms tumor in both cases
What is specific to the tumor suppressor gene inactivation mechanism?
You need to have BOTH alleles silenced for an oncogenic effect
Rb gene function, hereditary and sporadic neoplasms
- regulates cell cycle
- hereditary : retinoblastoma
- sporadic : retinoblastoma, lung cancer
p53 gene function, hereditary and sporadic neoplasms
- cell cycle block and apoptosis
- hereditary : li-fraumeni syndrome
- sporadic : most human cancers
APC gene function, hereditary and sporadic neoplasms
- beta katenin block
- hereditary : melanoma
- sporadic : colon cancer
