Multiple Endocrine Neoplasia Type 1: Clinical and Genetic Topics

Abstract

Multiple endocrine neoplasia type 1 (MEN1) consists of benign, and sometimes malignant, tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary, and other tissues. Skin angiofibromas and skin collagenomas are common. Typically, MEN1 tumors begin two decades earlier than sporadic tumors. Because of tumor multiplicity and the tendency for postoperative tumor recurrence, specialized methods have been developed for preoperative and intraoperative localization of many MEN1-associated tumors. The MEN1 gene was recently isolated by positional cloning. This strategy progressively narrows the size of the candidate MEN1 gene interval on the chromosome and then finds and tests many or, if needed, all genes within that interval. The MEN1 gene was finally identified because it was the one gene that contained mutations in most DNAs from a test panel of MEN1 cases. It has been suggested that MEN1, like many hereditary cancer syndromes, is caused by mutation in a tumor suppressor gene that contributes to neoplasia when both gene copies in a tumor precursor cell have been sequentially inactivated ("two-hit" oncogenesis mechanism). Germline MEN1 mutations were found in most families with MEN1 and in most cases of sporadic MEN1. In addition, the MEN1 gene was the gene most likely to show acquired mutation in several sporadic or nonhereditary tumors-parathyroid adenomas, gastrinomas, insulinomas, and bronchial carcinoids. Most germline or acquired MEN1 mutations predicted truncation (and thus likely inactivation) of the encoded protein, supporting expectations for the "first hit" to a tumor suppressor gene. Testing for MEN1 germline mutation is possible in a research setting. Candidates for MEN1 mutation testing include patients with MEN1 or its phenocopies and first-degree relatives of persons with MEN1.

Proliferation-Associated Expression of the MEN1 Gene as Revealed by In Situ Hybridization: Possible Role of the Menin as a Negative Regulator of Cell Proliferation Under DNA Damage

“…Despite its wide expression, involvement of menin is known only in endocrine tumors, foregut carcinoids, and cutaneous tumors (Bö ni et al, 1998;Marx et al, 1998). Additionally, the physiological significance of different levels of expression in different tissues is unclear.…”

Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors

“…3 Multiple endocrine neoplasia type-1 (MEN1) is an autosomal dominantly inherited disorder characterized by the development of multiple endocrine tumors including pancreatic endocrine tumors. 4 MEN1 results from germline mutations of MEN1, a 10-exon gene located on chromosome 11q13 that encodes for menin, a 610-amino-acid protein. 3,[5][6][7][8] Recent studies suggest menin regulates the transcription of multiple differentiation-regulating genes in association with a histone methyltransferase complex.…”

Case Report: A case report of acromegaly associated with primary aldosteronism

“…MEN1 is caused by germline mutations of the menin gene, which most frequently leads to the development of primary hyperparathyroidism, pituitary adenomas and pancreatic tumors. The prevalence of pituitary tumors in MEN1 varies according to different studies, from 10 to 76% 12– 14 . Somatotropinomas causing acromegaly occur in 3–6% of MEN1 patients 14, 15 .…”

“…The prevalence of pituitary tumors in MEN1 varies according to different studies, from 10 to 76% 12– 14 . Somatotropinomas causing acromegaly occur in 3–6% of MEN1 patients 14, 15 . As for adrenal involvement in patients with MEN1, the data are contradictory with a prevalence ranging from 9 to 73% depending on the investigated series 16– 18 .…”