The MEN1 gene and associated diseases: an update.

Heterozygous germline mutations of the tumor suppressor gene MEN1 are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited familial cancer syndrome characterized by the combined occurrence of pituitary, parathyroid, and enteropancreatic tumors. Various types of mutations likely causing loss of the gene function have been identified throughout the entire gene region in patients with MEN1 and related disorders including a small fraction of familial isolated hyperparathyroidism (FIHP). Neither mutation hot spot nor phenotype-genotype correlation has been established in classical MEN1, although some missense mutations may be specifically associated with a phenotype of FIHP. Familial isolated pituitary tumor and atypical familial MEN1 consisting of only pituitary tumor and hyperparathyroidism usually lack germline MEN1 mutations, suggesting that these familial endocrine tumor syndromes are genetic entities distinct from MEN1. DNA test for MEN1 germline mutations is a robust tool for diagnosis of predisposition to MEN1, and will be useful for the counseling and management of patients and their families. In this review, we will summarize the most recent findings on the MEN1 gene, focusing primarily on germline mutations and associated diseases.