A 45-year-old woman with endometrial carcinoma is found to have a germline mutation causing loss of MLH1. The mechanism of tumorigenesis is best described as:

• A Chromosomal instability from centrosome amplification
• B Promoter hypermethylation of RB1
• C Microsatellite instability due to defective mismatch repair ✓
• D Activation of oncogene by chromosomal translocation

Explanation

MLH1 is a mismatch repair (MMR) gene; germline mutations cause Lynch syndrome. MMR deficiency allows replication errors at microsatellite repeats to accumulate, producing microsatellite instability (MSI-H). This is distinct from chromosomal instability. RB1 hypermethylation is a somatic epigenetic event; translocations are oncogene-activating mechanisms seen in hematological malignancies.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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