Analysis of the MEN1 gene in sporadic pituitary adenomas

Abstract

The MEN1 gene on chromosome 11q13 is mutated in patients afflicted with multiple endocrine neoplasia syndrome type 1 (MEN1). These patients develop endocrine tumours of the pancreas, the parathyroid, and the anterior pituitary. In order to determine the role of MEN1 in sporadic pituitary adenomas, 61 pituitary adenomas were analysed from patients without evidence of a familial tumour syndrome. Single strand conformation polymorphism (SSCP) analysis was performed for the entire coding sequence of MEN1. Fragments with aberrant migration patterns were sequenced bidirectionally. Only a single somatic mutation was detected in this series. In addition, several previously reported and three novel polymorphisms were observed. Loss of heterozygosity analysis with 12 polymorphic markers, however, identified 13 pituitary adenomas with allelic deletions on chromosome 11. Allelic losses occurred significantly more often in pituitary adenomas with hormone secretion than in non-functioning adenomas. These data suggest that MEN1 mutations are rare events 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 chromosome 11 may suggest the presence of a yet unknown tumour suppressor gene, relevant to the pathogenesis of sporadic pituitary adenomas.