COMPARATIVE GENOMIC HYBRIDIZATION ANALYSIS OF NONFUNCTIONING PITUITARY-TUMORS

Clinically nonfunctioning pituitary adenomas constitute about one thir d of pituitary neoplasms and are considered monoclonal tumors. The mol ecular mechanisms of tumorigenesis in these neoplasms are poorly under stood, as evidenced by the paucity of reported somatic genetic alterat ions. Furthermore, the somatic mutations detected to date were primari ly ascribed to candidate genes or chromosomal regions: gsp, ras, p53 m utations, and allelic losses of 11q and 13q. To gain insight into whic h chromosomal regions bear genes involved in nonfunctioning pituitary tumorigenesis, we examined 23 such tumors by comparative genomic hybri dization. Four tumors showed no genetic abnormality, and the rest (17 of 23, 74%) exhibited at least one chromosomal region of abnormality. Gains and losses affected all chromosomes (except for chromosome 14). Notably, 8 of 23 tumors (34.7%) displayed sex chromosome and chromosom e 18 aberrations (amplifications or deletions). Nonrandom DNA amplific ation of subchromosomal regions on 4q, 5q (5q13-->5q23), 9p (9p21-->9p ter), 13q (13q21-->13q32), and 17q were detected in 10-30% of the tumo rs. Noteworthy, no tumor displayed deletion of 11q, the MEN1 gene locu s. These findings suggest that genes localized to previously undescrib ed chromosomal regions play a role in the tumorigenesis of nonfunction ing, pituitary adenomas.