Increased MEN1 mRNA expression in sporadic pituitary tumours

BACKGROUND The MEN1 gene on chromosome 11q13 encodes a tumour suppressor ge ne, mutations in which cause multiple endocrine neoplasia (MEN) type 1 synd rome. Loss of heterozygosity (LOH) at this locus is a common finding amongs t sporadic pituitary tumours, We have therefore screened the MEN1 gene for mutations in sporadic pituitary tumours and, as the gene is a putative tumo ur suppressor, have quantified mRNA expression in tumorous and normal pitui taries to assess the role of MEN1 in pituitary tumorigenesis. SUBJECTS AND DESIGN Thirty-one nonfunctioning pituitary tumours, 8 GH secre ting, 2 TSH-secreting tumours and 1 corticotrophinoma have been assessed fo r the presence of MEN1 mutations, to examine the hypothesis that MEN1 mutat ions may contribute to the pathogenesis of sporadic pituitary neoplasms. In addition, quantitative changes in the pretranslational expression of the t umour suppressor gene MEN1 have been determined in 42 pituitary tumours and 6 normal pituitaries using semiquantitative reverse transcriptase PCR. RESULTS No novel or previously published mutations were apparent in the MEN 1 coding regions of any tumours studied, although several polymorphisms wer e identified, Transcriptional changes of the gene, assessed by semiquantita tive RT-PCR, indicated that nonfunctioning and GH-secreting pituitary tumou rs are associated with significantly increased pretranslational expression of the MEN1 gene, In addition, the single corticotrophinoma showed increase d expression compared to normal, as did one of the two TSH-omas. CONCLUSION Coding mutations of the putative tumour suppressor gene MEN1 are unlikely to contribute to pituitary tumorigenesis in sporadic nonfunctioni ng, GH-secreting and TSH-secreting adenomas, Changes in pretranslational ex pression of MEN1 were observed in pituitary tumours, suggesting that change s in the level of MEN1 expression, rather than coding changes, may be of fu nctional importance in influencing sporadic pituitary tumorigenesis.