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.