ANALYSIS OF LOSS OF HETEROZYGOSITY ON CHROMOSOME-11 AND INFREQUENT INACTIVATION OF THE MEN1 GENE IN SPORADIC PITUITARY-ADENOMAS

To investigate the role of tumor suppressor genes in sporadic pituitar y adenomas, we first analyzed loss of heterozygosity on 11q13 with mic rosatellite analysis in 31 tumors. Loss of heterozygosity on 11q13 was detected in 1 mixed GH/PRL adenoma, and the somatic 22-bp deletion of the multiple endocrine neoplasia type 1 (MEN1) gene encoding menin wa s detected in this tumor. Trisomy 11 suggested by the decreased mean a llelic ratios of 66% or 65% for 16 or 13 microsatellite markers, respe ctively, in 2 of 31 pituitary adenomas was confirmed by interphase flu orescence in situ hybridization. Screening for mutations of the MEN1 g ene did not find mutations with PCR-single strand conformation polymor phism analysis in other pituitary adenomas retaining heterozygosity on 11q13. Based on these, it is concluded that inactivation of the MEN1 gene comprises a rare etiology for tumorigenesis of the pituitary glan d, and that trisomy 11 or another gene(s) may contribute to the pathog enesis of sporadic pituitary adenomas.