LOSS OF HETEROZYGOSITY AT 11Q13 - ANALYSIS OF PITUITARY-TUMORS, LUNG CARCINOIDS, LIPOMAS, AND OTHER UNCOMMON TUMORS IN SUBJECTS WITH FAMILIAL MULTIPLE ENDOCRINE NEOPLASIA TYPE-1

Loss of heterozygosity (LOH) for polymorphic markers flanking the mult iple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancre atic islet tumors from subjects with familial MEN-1 (FMEN-1) has been well documented and has led to the hypothesis that the MEN-1 gene func tions as a tumor suppressor. To assess the role of the MEN-1 gene in t he pathogenesis of tumors less commonly associated with MEN-1, we empl oyed a large number of highly informative polymorphic markers closely Licked to the MEN-1 gene to study a series of 13 such tumors from subj ects with FMEN-1 for LOH at 11q13. We were able to identify LOH for 1 or more 11q13 markers in 2 of 3 pituitary tumors, 3 lung carcinoids, a nd 1 of 2 lipomas. In every case studied, the allele lost represented the normal allele inherited from the unaffected parent. No LOH was det ected in 3 skin angiofibromas, an esophageal leiomyoma, or a renal ang iomyolipoma despite the presence of at least 2 informative markers for each tumor. Our results suggest that, like that for parathyroid and p ancreatic islet tumors, the pathogenesis of pituitary tumors, lung car cinoids, and lipomas occurring in subjects with FMEN-1 probably involv es loss of the normal tumor suppressor function of the MEN-1 gene. Our inability to detect 11q13 LOH in skin angiofibromas, leiomyoma, and a ngiomyolipoma from subjects with FMEN-1 is consistent with the possibi lity that these neoplasms arose independently by a mechanism unrelated to the MEN-1 gene, but a role for the MEN-1 gene in the pathogenesis of these tumors cannot be definitively excluded until the gene itself is identified and evaluated for small intragenic deletions or point mu tations in such tumors.