Neoplasia: neurofibromatosis type 1 molecular basis: practice question

A Pathology 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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Pathology · Neoplasia: neurofibromatosis type 1 molecular basis

Sample item

A 12-year-old has multiple café-au-lait macules, axillary freckling, Lisch nodules and cutaneous neurofibromas. Loss of function of which gene product explains the tumour predisposition?

AMenin, a transcriptional regulatorBNeurofibromin, a GTPase-activating protein for RASCTuberin, an inhibitor of mTOR signallingDMerlin, a cytoskeletal linking protein

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

The answer and the reasoning

B. Neurofibromin, a GTPase-activating protein for RAS

The NF1 gene on chromosome 17q encodes neurofibromin, which accelerates hydrolysis of RAS-GTP to inactive RAS-GDP. Loss keeps RAS active and drives proliferation, so NF1 acts as a tumour suppressor. Merlin is the NF2 protein, tuberin belongs to tuberous sclerosis, and menin to MEN1.

Option by option

A. Menin, a transcriptional regulator
Menin is mutated in MEN1, giving pituitary, parathyroid and pancreatic tumours.
B. Neurofibromin, a GTPase-activating protein for RAS (correct)
Correct. Neurofibromin normally switches RAS off, so its loss leaves RAS signalling on.
C. Tuberin, an inhibitor of mTOR signalling
Tuberin (TSC2) restrains mTOR and is mutated in tuberous sclerosis.
D. Merlin, a cytoskeletal linking protein
Merlin is the NF2 product and gives vestibular schwannomas.

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 Pathology question

What is the answer to this Pathology question?

The best answer is B, Neurofibromin, a GTPase-activating protein for RAS. The NF1 gene on chromosome 17q encodes neurofibromin, which accelerates hydrolysis of RAS-GTP to inactive RAS-GDP.

Why is "Menin, a transcriptional regulator" not the answer?

Menin is mutated in MEN1, giving pituitary, parathyroid and pancreatic tumours.

Why is "Tuberin, an inhibitor of mTOR signalling" not the answer?

Tuberin (TSC2) restrains mTOR and is mutated in tuberous sclerosis.

Why is "Merlin, a cytoskeletal linking protein" not the answer?

Merlin is the NF2 product and gives vestibular schwannomas.

What concept does this question test?

It tests Neoplasia: neurofibromatosis type 1 molecular basis in Pathology. Loss keeps RAS active and drives proliferation, so NF1 acts as a tumour suppressor. Merlin is the NF2 protein, tuberin belongs to tuberous sclerosis, and menin to MEN1.

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 Neoplasia: neurofibromatosis type 1 molecular basis?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology 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.