MUTATIONS OF THE MEN1 TUMOR-SUPPRESSOR GENE IN PITUITARY-TUMORS

Although pituitary adenomas are monoclonal proliferations, somatic mut ations involving genes that govern cell proliferation or hormone produ ction have been difficult to identify, The genetic etiology of most pi tuitary tumors, therefore, remains unknown. Pituitary adenomas can dev elop sporadically or as a part of multiple endocrine neoplasia type 1 (MEN1), Recently, the gene responsible for MEN1 was cloned, To elucida te the potential etiological role of the MEN1 gene in pituitary tumori genesis, 39 sporadic pituitary adenomas from 38 patients and 1 pituita ry adenoma from a familial MEN1 patient were examined for MEN1 gene mu tations and allelic deletions, Four of 39 sporadic pituitary adenomas showed a deletion of one copy of the MEN1 gene, and a specific MEN1 ge ne mutation in the remaining gene copy was detected in 2 of these tumo rs, The corresponding germ-line sequence was normal in all sporadic ca ses, A specific MEN1 mutation was detected in a pituitary adenoma and corresponding germ-line DNA in a patient with familial MEN1. An alleli c deletion of the remaining copy of the MEN1 gene was also found in th e patient's tumor. Genetic alterations of the MEN1 gene represent a ca ndidate pathogenetic mechanism of pituitary tumorigenesis, The data su ggest that somatic MEN1 gene mutations and deletions play a causative role in the development of a subgroup of sporadic pituitary adenomas.