Question

Patients with familial retinoblastoma carry a germline mutation in one copy of the Rb gene. Potential mechanisms for inactivation of the other allele in a retinoblastoma tumor arising in one of these patients include :

A. an independent point mutation

B. extra copy of the normal chromosome 13

C. overexpression of the Rb gene

D. loss of methylation of the promoter of Rb1 gene

E. A and D are correct

Answer 1

The answer will be an independent point mutation (Option A).

Explanation: Retinoblastoma developed due to the inactivation of both copies of RB1 gene which reside in chromosome 13. If there is an extra copy of the normal chromosome 13, it will have normal RB1 gene & will prevent to develop retinoblastoma & is not responsible for inactivation of the other allele. Over expression of the RB gene will prevent to develop retinoblastoma & is not responsible for inactivation of the other allele. DNA methylation in the promoter helps to repress gene transcription. So, loss of methylation in the promoter of Rb1 gene will help to transcribe RB1 gene & prevent to develop retinoblastoma. So, we can ignore options B, C, D & E. The probable reason that other allele is inactivated due to an independent point mutation. Thus, correct answer will be option A.