Medical genetics: two-hit hypothesis: practice question

A Anatomy question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Anatomy · Medical genetics: two-hit hypothesis

Sample item

Children who inherit one mutant RB1 allele usually develop multiple bilateral retinoblastomas, whereas sporadic cases usually have a single unilateral tumour. What explains the difference?

AInherited cases have a duplication of chromosome 13BThe inherited allele acts as a gain-of-function oncogeneCEvery retinoblast starts with one hit and needs one moreDSporadic cases need a germline RB1 mutation first

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

The answer and the reasoning

C. Every retinoblast starts with one hit and needs one more

In Knudson's two-hit model, children with a germline mutation have one defective RB1 allele in every retinal cell, so a single somatic hit in any cell causes a tumour. In sporadic cases both hits must occur in the same cell, which makes tumours later, fewer and unilateral.

Option by option

A. Inherited cases have a duplication of chromosome 13
The mechanism is loss of a tumour suppressor allele, not a chromosome 13 duplication.
B. The inherited allele acts as a gain-of-function oncogene
RB1 is a tumour suppressor gene and loss of function, not gain of function, is required.
C. Every retinoblast starts with one hit and needs one more (correct)
Correct. A single further somatic hit in any of many cells makes multiple early tumours likely.
D. Sporadic cases need a germline RB1 mutation first
Sporadic cases arise from two somatic hits and have no germline mutation.

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.

Questions about this Anatomy question

What is the answer to this Anatomy question?

The best answer is C, Every retinoblast starts with one hit and needs one more. In Knudson's two-hit model, children with a germline mutation have one defective RB1 allele in every retinal cell, so a single somatic hit in any cell causes a tumour.

Why is "Inherited cases have a duplication of chromosome 13" not the answer?

The mechanism is loss of a tumour suppressor allele, not a chromosome 13 duplication.

Why is "The inherited allele acts as a gain-of-function oncogene" not the answer?

RB1 is a tumour suppressor gene and loss of function, not gain of function, is required.

Why is "Sporadic cases need a germline RB1 mutation first" not the answer?

Sporadic cases arise from two somatic hits and have no germline mutation.

What concept does this question test?

It tests Medical genetics: two-hit hypothesis in Anatomy. In sporadic cases both hits must occur in the same cell, which makes tumours later, fewer and unilateral.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Medical genetics: two-hit hypothesis?

Learn every nerve by its route, its muscles and what a lesion looks like at the bedside. That one habit answers a large share of questions. Then use the flashcards and the other Anatomy questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.