MUTATION OF THE MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 GENE IN NONFAMILIAL, MALIGNANT-TUMORS OF THE ENDOCRINE PANCREAS

Endocrine pancreatic tumors are rare neoplasms that occur sporadically or as part of a multiple endocrine neoplasia type 1 (MEN1) syndrome. Germ-line mutations of the MEN1 gene, located at 11q13, have been demo nstrated in MEN1 kindreds, and loss of heterozygosity (LOH) on 11q13 t ogether with somatic MEN1 mutations have been detected in 20% of nonfa milial parathyroid tumors. Here, we examine 11 non-MEN1 malignant tumo rs of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagono mas. LOH of at least one informative locus on 11q13 was found in 70% o f the tumors. Three tumors displayed somatic mutations of the MEN1 gen e together with LOH on 11q13, whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MEN1 gene mutat ions contribute to the tumorigenesis of nonfamilial, malignant endocri ne pancreatic tumors.