MEN2A (Multiple Endocrine Neoplasia type 2A) involves medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. The causative mutation is:

• A Activating point mutation in the RET proto-oncogene (receptor tyrosine kinase) ✓
• B Inactivating mutation of MEN1 tumor suppressor gene on chromosome 11q13
• C Inactivating mutation in VHL gene causing constitutive HIF activation
• D Activating mutation in GNAS (Gs-alpha) causing constitutive cAMP production

Explanation

MEN2A and MEN2B are caused by activating germline point mutations in the RET proto-oncogene encoding a receptor tyrosine kinase. In MEN2A, mutations most commonly affect the extracellular cysteine residues (codon 634), causing constitutive RET dimerization and activation. In MEN2B, the most common mutation is M918T in the kinase domain. MEN1 (inactivating, chromosome 11q13) causes MEN1 syndrome. VHL mutations cause von Hippel-Lindau. GNAS mutations cause McCune-Albright syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.