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Localization of the Multiple Endocrine Neoplasia Type I (MEN1) Gene Based on Tumor Loss of Heterozygosity Analysis

Laboratory of Pathology, National Cancer Institute [M. R. E-B., I. A. L., Z. Z., L. A. L., L. V. D.]; Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases [Q. D., M. B. K., S. A., A. L. B., A. M. S., S. J. M.]; and National Human Genome Research Institute [P. M., S. C. G., S-E. O., F. S. C., S. C. C.], Bethesda, Maryland 20892

Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors as well as foregut carcinoids in affected patients. The gene responsible for the disease has been linked to chromosome 11q13. We analyzed loss of heterozygosity (LOH) in 188 tumors from 81 patients in an attempt to further define the location of the MEN1 gene. Both tumors from MEN1 patients and corresponding sporadic tumors were analyzed. Tumor types included parathyroid, gastrinoma, pancreatic endocrine, pituitary, and lung carcinoid. Six tumors (three MEN1 and three sporadic tumors) were identified that provided important LOH boundaries. Four tumors (two parathyroid tumors, one gastrinoma, and one lung carcinoid tumor) showed allelic loss that placed the MEN1 gene distal to marker PYGM. Two tumors (one gastrinoma and one parathyroid tumor) showed an LOH boundary that placed the gene proximal to D11S449, one of which further moved the telomeric boundary to D11S4936. Taken together, the present data suggest that the MEN1 gene lies between PYGM and D11S4936, a region of approximately 300 kb on chromosome 11q13.

¹ To whom requests for reprints should be addressed, at Laboratory of Pathology, National Cancer Institute, Bldg. 10, Rm. 2A33, 9000 Rockville Pike, Bethesda, MD 20892.

Received 2/20/97. Accepted 4/ 2/97.

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