Mutation of the Multiple Endocrine Neoplasia Type 1 Gene in Noni umiliai, Malignant Tumors of the Endocrine Pancreas1

Endocrine pancreatic tumors are rare neoplasms that occur sporadi cally or as part of a multiple endocrine neoplasia type 1 (MENI) syn drome. Germ-line mutations of the MENI gene, located at Ilql3, have been demonstrated in MENI kindreds, and loss of heterozygosity (LOH) on I lt/1,1 together with somatic MENI mutations have been detected in 20% of nonfamilial parathyroid tumors. Here, we examine 11 non-MENl malignant tumors of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagonomas. LOH of at least one informative locus on //.whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MENI gene mutations contribute to the tumorigenesis of nonfamilial, malignant endocrine pancreatic tumors.