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NEOPLASIA 3: TUMOR SUPPRESSOR GENES: Retinoblastoma Gene, Knudson's Two Hit Hypothesis.

This short tutorial explains the general concepts of tumor suppressor genes and a detailed explaination of Retinoblastoma gene ***Follow me**** http://ilovepathology.com/ Twitter :   / vijaypatho     / ilovepathology2   Facebook:   / ilovepathology   Tumor suppression genes- general aspects Retinoblastoma gene Knudson’s two Hit Hypothesis Role of RB in regulation of cell cycle Mechanism of inactivation of RB Tumors associated with RB gene mutations 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 ~-~~-~~~-~~-~ Please watch: "WARBURG EFFECT: Hallmark of CANCER. What, Why & How?"    • NEOPLASIA 6: WARBURG EFFECT: Hallmark...   ~-~~-~~~-~~-~