<prompt> Knudsons two hit hypothesis is characteristically associated with?NeuroblastomaMelanomaRetinoblastomaRCC  <response>: Ans is c i.e. Retinoblastoma Retinoblastoma is a typical example of Knudsons two hit hypothesisKnudson hypothesis two-hit hypothesis or multiple-hit hypothesis It says that cancer is the result of accumulated mutations to a cells DNA. Knudsons hypothesis refers specifically to the heterozygosity of tumor suppressor genes. RB gene is a tumor suppressor gene typical example of this hypothesis. Knudson noted that inherited retinoblastoma occurs at a younger age than the sporadic disease. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition he suggested that multiple hits to DNA were necessary to cause cancer. Retinoblastoma develops when both the normal alleles of the RB genes are inactive or altered. In Hereditary retinoblastoma first genetic change first hit in RB gene is inherited from an affected parent, where as second mutation second hit occurs in postnatal life and both alleles are lost. In non- hereditary retinoblastoma, both mutations first and second hits occur postnataly. 