Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is caused by germline mutations in genes encoding proteins of the mismatch repair (MMR) system. The hallmark molecular finding in MMR-deficient tumors is:

• A Microsatellite instability (MSI) ✓
• B Loss of heterozygosity at tumor suppressor loci
• C CpG island hypermethylation of the promoter
• D Chromosomal translocations creating fusion oncoproteins

Explanation

Mismatch repair proteins (MSH2, MLH1, MSH6, PMS2) recognize and correct insertion-deletion loops that form at simple sequence repeats (microsatellites) during DNA replication. When MMR is defective, these short tandem repeats accumulate insertions or deletions, producing novel allele sizes detectable by PCR — microsatellite instability. MSI is the molecular signature used both to diagnose Lynch syndrome and to predict response to immune checkpoint inhibitor therapy in colorectal cancer.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.