MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 AND THE SEARCH FOR THE GENETIC TRIGGER

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by primar y hyperparathyroidism, endocrine pancreatic-duodenal and anterior pitu itary tumors. The diagnosis is challenging and involves the exclusion of other endocrine neoplasia syndromes with overlapping features. The predisposing genetic defect was assigned to chromosomal region 11q13 b ased on linkage analysis. Combined tumor and pedigree genotype analysi s showed that allele losses in pancreatic, parathyroid and pituitary t umors eliminated the wild-type allele at the 11q13 loci, suggesting in activation of a tumor suppressor gene in this region. A 5-Mb integrate d map of the region has been established by the European consortium on MEN-1. Based on this mapping the critical interval was restricted to 2 Mb, a region within which eight candidate genes are located.