Neoplasia: oncogene activation by amplification: 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: oncogene activation by amplification

Sample item

A 2-year-old child has an abdominal mass with raised urinary VMA and HVA. Biopsy shows small round blue cells forming Homer-Wright rosettes, and karyotype shows double minutes and homogeneously staining regions. Which genetic alteration, associated with poor prognosis, do these findings indicate?

AEWS-FLI1 fusion from t(11;22)BActivating point mutation of RETCDeletion of WT1 at 11p13DAmplification of MYCN

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

The answer and the reasoning

D. Amplification of MYCN

Double minutes and homogeneously staining regions are cytogenetic signs of gene amplification. In neuroblastoma, MYCN amplification on chromosome 2p is linked to advanced stage and poor outcome. Amplification of HER2 in breast cancer works by the same mechanism.

Option by option

A. EWS-FLI1 fusion from t(11;22)
The EWS-FLI1 fusion characterises Ewing sarcoma, a bone and soft tissue tumour without catecholamine excretion.
B. Activating point mutation of RET
RET point mutations cause medullary thyroid carcinoma in MEN 2, not neuroblastoma.
C. Deletion of WT1 at 11p13
WT1 deletion predisposes to Wilms tumour, a renal tumour with blastemal, stromal and epithelial elements.
D. Amplification of MYCN (correct)
MYCN amplification explains double minutes and homogeneously staining regions in neuroblastoma.

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 D, Amplification of MYCN. Double minutes and homogeneously staining regions are cytogenetic signs of gene amplification.

Why is "EWS-FLI1 fusion from t(11;22)" not the answer?

The EWS-FLI1 fusion characterises Ewing sarcoma, a bone and soft tissue tumour without catecholamine excretion.

Why is "Activating point mutation of RET" not the answer?

RET point mutations cause medullary thyroid carcinoma in MEN 2, not neuroblastoma.

Why is "Deletion of WT1 at 11p13" not the answer?

WT1 deletion predisposes to Wilms tumour, a renal tumour with blastemal, stromal and epithelial elements.

What concept does this question test?

It tests Neoplasia: oncogene activation by amplification in Pathology. In neuroblastoma, MYCN amplification on chromosome 2p is linked to advanced stage and poor outcome. Amplification of HER2 in breast cancer works by the same mechanism.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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: oncogene activation by amplification?

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.