Neoplasia: von Hippel-Lindau syndrome: 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: von Hippel-Lindau syndrome

Sample item

A 32-year-old man has retinal and cerebellar haemangioblastomas and bilateral clear cell renal carcinomas, and his father had similar tumours. How does loss of the product of the responsible tumour suppressor gene promote tumour growth?

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

The answer and the reasoning

A. HIF-1 alpha is not degraded, so VEGF and PDGF are overexpressed

The VHL protein is part of a ubiquitin ligase complex that targets hypoxia-inducible factor 1 alpha for degradation when oxygen is present. When VHL is lost, HIF accumulates even in normoxia and drives transcription of VEGF, PDGF and glycolytic genes, giving the hypervascular tumours of this syndrome.

Option by option

  • A. HIF-1 alpha is not degraded, so VEGF and PDGF are overexpressed (correct)

    HIF accumulation with VEGF and PDGF excess underlies the vascular tumours of VHL disease.

  • B. Rb remains hypophosphorylated, so E2F is sequestered and cells arrest

    A hypophosphorylated Rb holding E2F would restrain the cell cycle, which is the opposite of tumour growth.

  • C. RAS stays GTP-bound because the GTPase activating protein is lost

    Loss of a RAS GTPase activating protein describes NF1, whose neurofibromin product is a RAS-GAP.

  • D. Mismatch repair fails, causing widespread microsatellite instability

    Mismatch repair failure is the mechanism of Lynch syndrome, not VHL disease.

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.

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Questions about this Pathology question

What is the answer to this Pathology question?

The best answer is A, HIF-1 alpha is not degraded, so VEGF and PDGF are overexpressed. The VHL protein is part of a ubiquitin ligase complex that targets hypoxia-inducible factor 1 alpha for degradation when oxygen is present.

Why is "Rb remains hypophosphorylated, so E2F is sequestered and cells arrest" not the answer?

A hypophosphorylated Rb holding E2F would restrain the cell cycle, which is the opposite of tumour growth.

Why is "RAS stays GTP-bound because the GTPase activating protein is lost" not the answer?

Loss of a RAS GTPase activating protein describes NF1, whose neurofibromin product is a RAS-GAP.

Why is "Mismatch repair fails, causing widespread microsatellite instability" not the answer?

Mismatch repair failure is the mechanism of Lynch syndrome, not VHL disease.

What concept does this question test?

It tests Neoplasia: von Hippel-Lindau syndrome in Pathology. When VHL is lost, HIF accumulates even in normoxia and drives transcription of VEGF, PDGF and glycolytic genes, giving the hypervascular tumours of this syndrome.

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: von Hippel-Lindau syndrome?

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.