Tumour suppressors: retinoblastoma: practice question

Try it

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Every retinoblast already carries one mutant RB1 allele, so a single somatic hit in each cell removes the remaining normal copy

Knudson's two-hit hypothesis states that both RB1 alleles must be lost. In hereditary disease the first hit is a germline mutation present in every cell, so only one somatic hit is needed in any of many retinoblasts, giving early, multifocal and bilateral tumours. Survivors have a high risk of osteosarcoma and other second cancers.

Option by option

• A. Every retinoblast already carries one mutant RB1 allele, so a single somatic hit in each cell removes the remaining normal copy (correct)

  A germline first hit leaves only one somatic event required, so tumours arise earlier and in both eyes.

• B. A dominant-negative RB protein inactivates the normal protein in the same cell

  RB1 acts as a recessive tumour suppressor at the cellular level, not through dominant-negative action.

• C. Amplification of the MYC oncogene drives tumour formation

  MYC amplification is not the cause of retinoblastoma, and the inherited form involves germline RB1 loss.

• D. Two separate somatic mutations are required in each retinoblast, as in sporadic disease

  Two somatic hits in the same cell are needed in sporadic disease, which is therefore unilateral and later.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

More Biochemistry questions