Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome) results from germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2). The diagnostic hallmark on tumor tissue analysis is:
- A Loss of heterozygosity (LOH) at chromosome 5q
- B CpG island methylator phenotype (CIMP)
- C Microsatellite instability (MSI-H) ✓
- D BRAF V600E mutation
Correct answer: C. Microsatellite instability (MSI-H)
Explanation
Mismatch repair (MMR) corrects single-base mismatches and insertion-deletion loops at repetitive microsatellite sequences. When MMR is deficient, microsatellites accumulate insertion/deletion mutations — a phenotype called microsatellite instability (MSI-H, high). MSI-H testing (by PCR of BAT-25, BAT-26 markers) and IHC for MMR protein loss are the standard diagnostic workup for Lynch syndrome. LOH at 5q is characteristic of familial adenomatous polyposis (APC gene). BRAF V600E marks sporadic MSI-H tumors.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.