A 45-year-old woman undergoes colectomy for adenocarcinoma. Molecular testing shows microsatellite instability with loss of expression of MLH1 by immunohistochemistry. The defective process underlying this tumour is:

• A Nucleotide excision repair of bulky DNA adducts
• B Homologous recombination repair of double-strand breaks
• C Base excision repair of deaminated bases by glycosylases
• D Correction of base-base mismatches and small insertion-deletion loops during replication ✓

Explanation

Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) correct replication errors such as single-base mismatches and small insertion-deletion loops, particularly in microsatellite regions. Loss of this repair produces microsatellite instability, the hallmark of Lynch syndrome cancers. Nucleotide excision repair defects cause xeroderma pigmentosum, and homologous recombination defects are linked to BRCA-associated breast and ovarian cancer, not MSI.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.