Somatic MEN1 gene mutation does not contribute significantly to sporadic pituitary tumorigenesis

Pituitary adenomas are a common manifestation of multiple endocrine neoplas ia type 1 (MEN1) but most of them occur sporadically There are only a few w ell defined genetic abnormalities known to occur in these sporadic tumours. The MEN1 gene located on 11q13 has recently been cloned and allelic deleti on and mutation analysis studies have implicated the MEN1 gene in a signifi cant fraction of the sporadic counterparts of typical MEN1 neoplasms (parat hyroid tumours, insulinomas and gastrinomas). To determine if MEN1 gene inactivation is also involved in the development of sporadic pituitary adenomas, allelic deletions of chromosome 11q13 and M EN1 gene mutations and polymorphisms were assessed in 35 sporadic tumours o f the anterior pituitary (9 prolactin-secreting, 8 GH-secreting, 3 TSH-secr eting, 2 TSH/GH-secreting, 4 Cushing, 9 silent). Thirty-one tumours were fo und to be heterozygous for at least one MEN1 intragenic polymorphism (25 ca ses) or for a flanking gene polymorphism (6 cases). The remaining tumours w ere not informative. No mutations were found in any tumour except in one prolactinoma which was homozygous or hemizygous for a mutation (1-117 C --> T) in a region close t o the promoter. Unfortunately, brood or normal tissue was not available in this case, Our data show that somatic MEN1 mutations do not contribute significantly t o tumorigenesis of sporadic pituitary adenomas and suggest that mutation of other genes are likely to contribute to the pathogenesis of these tumours.