Lynch syndrome is caused by germline mutations in DNA mismatch repair genes. Which molecular hallmark is characteristic of tumors arising in this syndrome?

• A Microsatellite instability ✓
• B Chromosomal instability with aneuploidy
• C BRCA1/2 mutation with homologous recombination deficiency
• D Philadelphia chromosome with BCR-ABL fusion

Explanation

Lynch syndrome results from germline mutations in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2. Loss of mismatch repair leads to accumulation of errors in repetitive DNA sequences called microsatellites, producing microsatellite instability. This is the molecular hallmark used for screening. Chromosomal instability is typical of sporadic colorectal cancer via the APC pathway. BRCA mutations cause homologous recombination deficiency in breast and ovarian cancer.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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