MEN1 GENE-MUTATIONS IN 12 MEN1 FAMILIES AND THEIR ASSOCIATED TUMORS

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant in herited tumor syndrome characterized by the development of multiple en docrine tumors. The gene responsible for the disease, termed MEN1 gene , has recently been isolated and germline mutations have been describe d in affected MEN1 individuals. Twelve unrelated German MEN1 families and their associated tumors (5 parathyroid tumors, 1 vipoma, 1 gastrin oma, 1 insulinoma) were characterized for MEN1 gene mutations by singl e-strand conformational variant (SSCV) analysis and DNA sequence analy sis as well as for loss of heterozygosity on chromosome 11q13. We iden tified nine different heterozygous germline mutations (6 frameshift, 2 missense, 1 nonsense), eight of them were novel. Four of five informa tive MEN1-associated tumors revealed deletion of the second MEN1 allel e, supporting the concept of a tumor suppressor gene. Furthermore, SSC V analysis proved an effective and sensitive method far the detection of menin mutations providing a reliable genetic screening approach sup porting genetic counseling and clinical management of MEN1 family memb ers.