This short tutorial explains the general concepts of tumor suppressor genes and a detailed explaination of Retinoblastoma gene
Tumor suppressor proteins( products of TSG)
Regulate cell growth by applying brakes to cell proliferation ( Growth Inhibition)
Failure of growth inhibition is seen in carcinogenesis
Loss of function of these genes is a key event in carcinogenesis
Retinoblastoma Gene ( RB Gene)
First discovered Tumor suppressor gene
Chromosome 13q14
Retinoblastoma: is a childhood tumor with inactivation of this gene.
Knudson’s two-hit hypothesis
Two mutations ( hits) involving both the alleles of TSG ( here RB gene) is a basic requisite for the development of tumor
Retinoblastoma can occur as hereditary or sporadic form
Explanation for the same is given by Knudson’s two-hit hypothesis
RB protein– product of RB gene
Key role in regulation of the cell cycle
“Governor” of the cell cycle
So, How does RB gets inactivated ?OrHow does the Antiproliferative activity of RB is nullified?
1. Germline & somatic loss of function Mutations of RB Gene
2. Gene Amplifications of CDK 4 and Cyclin D genes
3. Functional inactivation of RB
Tumors associated with RB Gene mutations
Retinoblastoma
Osteosarcoma
Glioblastomas
Small cell carcinomas of lung
Breast cancers &
Bladder cancers
