Colorectal: Lynch syndrome: practice question

A General Surgery 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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General Surgery · Colorectal: Lynch syndrome

Sample item

A 38-year-old man has a right-sided colon adenocarcinoma. His mother had endometrial cancer and a maternal uncle had colon cancer, both before 50. Immunohistochemistry of the tumour shows loss of MSH2 and MSH6 staining. What is the underlying molecular mechanism?

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

The answer and the reasoning

B. Defective DNA mismatch repair causing microsatellite instability

Lynch syndrome (hereditary non-polyposis colorectal cancer) is autosomal dominant, caused by germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Failure to correct replication errors produces microsatellite instability and early right-sided colon cancers with a high risk of endometrial and other cancers. Tumours show loss of the corresponding mismatch repair proteins on immunohistochemistry.

Option by option

  • A. Mutation of STK11 causing unchecked mTOR signalling

    STK11 mutation causes Peutz-Jeghers syndrome and does not give mismatch repair protein loss.

  • B. Defective DNA mismatch repair causing microsatellite instability (correct)

    Loss of mismatch repair protein staining reflects the mismatch repair defect and microsatellite instability.

  • C. Loss of the APC tumour suppressor gene causing chromosomal instability

    APC loss drives the chromosomal instability pathway of familial adenomatous polyposis, with hundreds of polyps.

  • D. Defective base excision repair due to biallelic MUTYH mutation

    MUTYH-associated polyposis is autosomal recessive and presents with multiple polyps, not this dominant pedigree.

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 General Surgery question

What is the answer to this General Surgery question?

The best answer is B, Defective DNA mismatch repair causing microsatellite instability. Lynch syndrome (hereditary non-polyposis colorectal cancer) is autosomal dominant, caused by germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2).

Why is "Mutation of STK11 causing unchecked mTOR signalling" not the answer?

STK11 mutation causes Peutz-Jeghers syndrome and does not give mismatch repair protein loss.

Why is "Loss of the APC tumour suppressor gene causing chromosomal instability" not the answer?

APC loss drives the chromosomal instability pathway of familial adenomatous polyposis, with hundreds of polyps.

Why is "Defective base excision repair due to biallelic MUTYH mutation" not the answer?

MUTYH-associated polyposis is autosomal recessive and presents with multiple polyps, not this dominant pedigree.

What concept does this question test?

It tests Colorectal: Lynch syndrome in General Surgery. Failure to correct replication errors produces microsatellite instability and early right-sided colon cancers with a high risk of endometrial and other cancers. Tumours show loss of the corresponding mismatch repair proteins on immunohistochemistry.

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 Colorectal: Lynch syndrome?

Learn classic signs and eponyms alongside what they diagnose. Then use the flashcards and the other General Surgery 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.