Question

The two-hit model/mechanism for tumor causation?

Answer 1

'two hit hypothesis ' of oncogenesis is proposed by Knudson. In regards to a cancer called retinoblastoma.

RB gene , retinoblastoma gene, is a tumor suppressor gene. It contains two allele .

- Two mutations ( hits ) , involving both alleles of RB are required to produce retinoblastoma.

- In familial cases , children inherit on defective copy of the RB gene in the germline ( the first hit ) and the other copy is normal. Retinoblastoma develops when the normal RB allele is mutated in retinoblasts as a result of spontaneous somatic mutations ( the second hit ).

- in sporadic ceses both normal RB alleles must undergo somatic mutation in the same retinoblasts( two hits ).

- The two hit model basically says that two mutations are necessary in the RB gene , one in each allele , to develope retinoblastoma , a cancer of retinal cell.

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