Which gene mutation is associated with MEN2?

Which gene mutation is associated with MEN2?

• A. RET mutation
• B. MEN1 gene
• C. BRCA1
• D. TP53

Answer: (A)

Activating mutations in the RET proto-oncogene are what drive MEN2. RET encodes a receptor tyrosine kinase essential for development of neural crest–derived tissues, and gain-of-function changes cause constitutive signaling that promotes medullary thyroid carcinoma, pheochromocytoma, and related parathyroid abnormalities seen in MEN2. Because this inheritance is autosomal dominant, a person with the mutation has a high risk, and identifying RET mutations allows early management, such as prophylactic thyroidectomy in high-risk mutations, to prevent or reduce medullary thyroid cancer. The other genes listed are linked to different syndromes: MEN1 gene causes MEN1, BRCA1 is associated with breast/ovarian cancer risk, and TP53 with Li-Fraumeni–type cancers.

Activating mutations in the RET proto-oncogene are what drive MEN2. RET encodes a receptor tyrosine kinase essential for development of neural crest–derived tissues, and gain-of-function changes cause constitutive signaling that promotes medullary thyroid carcinoma, pheochromocytoma, and related parathyroid abnormalities seen in MEN2. Because this inheritance is autosomal dominant, a person with the mutation has a high risk, and identifying RET mutations allows early management, such as prophylactic thyroidectomy in high-risk mutations, to prevent or reduce medullary thyroid cancer. The other genes listed are linked to different syndromes: MEN1 gene causes MEN1, BRCA1 is associated with breast/ovarian cancer risk, and TP53 with Li-Fraumeni–type cancers.