Menin is ubiquitously expressed in both endocrine and nonendocrine tissues and does not display significant homology to any known family of proteins. The MEN1 gene consists of ten exons spanning 9 kb of genomic DNA and encodes a 610-amino acid protein product termed menin. In addition, a variety of sporadic endocrine tumors, such as parathyroid adenomas, pancreatic insulinomas and pituitary prolactinomas, have expressed somatic mutations and loss of heterozygosity of the MEN1 alleles, demonstrating that the MEN1 gene may play the same role in nonhereditary endocrine tumors. This phenomenon has suggested a role of MEN1 as a tumor suppressor gene, requiring inactivation of both alleles for clonal expansion and tumor development. In patients affected with MEN-1 syndrome, the presence of MEN1 germline mutations accompanied by loss of heterozygosity at 11q13 is observed. First proposed by Knudson to describe the tumorigenesis of retinoblastomas, the two-hit hypothesis for tumor suppressor genes also applies to MEN-1 syndrome. It is characterized by parathyroid hyperplasia, anterior pituitary adenomas and tumors of the endocrine pancreas and duodenum. Formerly known as Wermer’s syndrome, MEN-1 syndrome is an autosomal dominant disorder associated with mutations in the MEN1 gene mapped to chromosome 11q13. Insulinomas can occur sporadically or in conjunction with MEN-1 syndrome.
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