What is the pathophysiology of multiple endocrine neoplasia type 1 (MEN1)

Updated: Sep 14, 2018
  • Author: Thomas N Darling, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Answer

Patients with MEN1 inherit a mutation in a tumor suppressor gene called MEN1 on chromosome band 11q13. [6, 7] This gene encodes a 610-amino acid protein, menin, that regulates transcription, proliferation, and genome stability. Menin appears to be located mostly in the nucleus, where it has multiple binding partners, including junD and histone modifiers. [8, 9, 10] A mutant menin has been shown to be defective for the transforming growth factor-beta signaling pathway. [11]

Tumor formation involves inactivating mutations of both alleles of the MEN1 gene. In people without MEN1, two independent somatic mutations must occur within a single cell for tumor formation. In an individual with MEN1 , the first mutation is already present in all of the patient's cells, so that only a single somatic mutation is required. This accounts for the multiple tumors and the tumors occurring at an earlier age. Second-hit mutations in MEN1 have been documented in angiofibromas, collagenomas, and lipomas in patients with MEN1. [12, 13, 14]


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