Analysis of the MEN1 gene in sporadic pituitary adenomas

The MEN1 gene on chromosome 11q13 is mutated in patients afflicted with mul tiple endocrine neoplasia syndrome type 1 (MEN1). These patients develop en docrine tumours of the pancreas, the parathyroid, and the anterior pituitar y. In order to determine the role of MEN1 in sporadic pituitary adenomas, 6 1 pituitary adenomas were analysed from patients without evidence of a fami lial tumour syndrome. Single strand conformation polymorphism (SSCP) analys is was performed for the entire coding sequence of MEN1. Fragments with abe rrant migration patterns were sequenced bidirectionally. Only a single soma tic mutation was detected in this series. In addition, several previously r eported and three novel polymorphisms were observed. Loss of heterozygosity analysis with 12 polymorphic markers, however, identified 13 pituitary ade nomas with allelic deletions on chromosome 11. Allelic losses occurred sign ificantly more often in pituitary adenomas with hormone secretion than in n on-functioning adenomas. These data suggest that MEN1 mutations are rare ev ents in sporadic pituitary adenomas. However, the discrepancy of only 1/61 adenomas with MEN1 mutation but 13/61 (22 per cent) with allelic loss on ch romosome 11 may suggest the presence of a yet unknown tumour suppressor gen e, relevant to the pathogenesis of sporadic pituitary adenomas. Copyright ( C) 1999 John Whey & Sons, Ltd.