Cytogenetic and genomic studies of uterine leiomyomas have identified recurrent driver alterations. Which molecular alteration is found in the LARGEST proportion of conventional karyotype-normal leiomyomas?

• A KRAS activating mutation
• B t(12;14)(q15;q24) translocation involving HMGA2
• C BRCA1 germline mutation
• D Somatic mutation of the MED12 gene ✓

Explanation

About 70% of karyotypically normal leiomyomas carry somatic MED12 mutations on chromosome Xq13, making it the single most common genetic alteration in these tumours. The t(12;14) translocation dysregulating HMGA2 accounts for a smaller subset, roughly 10 to 15%. BRCA1 mutations predispose to breast and ovarian cancer, and KRAS mutations are typical of pancreatic and colorectal malignancies rather than fibroids.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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