Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is caused by germline mutations in mismatch repair (MMR) genes. The revised Bethesda guidelines recommend MMR testing on tumour tissue if the patient is diagnosed with CRC under age 50. Which mutation accounts for the LARGEST proportion of Lynch syndrome cases?
- A MSH2
- B MLH1 ✓
- C MSH6
- D PMS2
Correct answer: B. MLH1
Explanation
MLH1 mutations account for approximately 40–50% of Lynch syndrome cases, making it the most commonly affected MMR gene, followed by MSH2 (~35–40%). MSH6 and PMS2 together comprise a minority. MLH1 hypermethylation (epigenetic silencing) is also the most common cause of sporadic MSI-High CRC, and somatic BRAF V600E mutation distinguishes sporadic MSI-H from Lynch syndrome.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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