Comparative genomic hybridization analysis of nonfunctioning pituitary tumors

Clinically nonfunctioning pituitary adenomas constitute about one third of pituitary neoplasms and are considered monoclonal tumors. The molecular mechanisms of tumorigenesis in these neoplasms are poorly understood, as evidenced by the paucity of reported somatic genetic alterations. Furthermore, the somatic mutations detected to date were primarily ascribed to candidate genes or chromosomal regions: gsp, ras, p53 mutations, and allelic losses of 11q and 13q. To gain insight into which chromosomal regions bear genes involved in nonfunctioning pituitary tumorigenesis, we examined 23 such tumors by comparative genomic hybridization. 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 chromosome 18 aberrations (amplifications or deletions). Nonrandom DNA amplification of subchromosomal regions on 4q, 5q (5q13-->5q23), 9p (9p21-->9pter), 13q (13q21-->13q32), and 17q were detected in 10-30% of the tumors. Noteworthy, no tumor displayed deletion of 11q, the MEN1 gene locus. These findings suggest that genes localized to previously undescribed chromosomal regions play a role in the tumorigenesis of nonfunctioning, pituitary adenomas.