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

Departments of Surgery [O. H., D. L., T. C., P. H., J. R., G. Å., G. W.] and Internal Medicine [B. S.], University Hospital, S-751 85 Uppsala, Sweden

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 demonstrated in MEN1 kindreds, and loss of heterozygosity (LOH) on 11q13 together with somatic MEN1 mutations have been detected in 20% of nonfamilial parathyroid tumors. Here, we examine 11 non-MEN1 malignant tumors of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagonomas. LOH of at least one informative locus on 11q13 was found in 70% of the tumors. Three tumors displayed somatic mutations of the MEN1 gene together with LOH on 11q13, whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MEN1 gene mutations contribute to the tumorigenesis of nonfamilial, malignant endocrine pancreatic tumors.

¹ This work was supported by grants from the Swedish Medical Research Council, the Swedish Cancer Society, the Torsten and Ragnar Söderbergs Research Foundation, and Lions Fund for Cancer Research. Primers for LOH analysis were provided by the Dept. of Clinical Genetics, Uppsala University supported by the Council of the Nordic Ministers and the Swedish Medical Research Council.

² O. H. and D. L. contributed equally to this work.

³ To whom requests for reprints should be addressed. Fax: 46-18-553601; E-mail: ola.hessman@kirurgi.uu.se.

Received 10/13/97. Accepted 12/19/97.

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