title: Clinically nonfunctioning pituitary tumors are monoclonal in origin.
abstract: Clinically nonfunctioning pituitary adenomas are benign neoplasms comprising approximately 25-30% of pituitary tumors. Little is known about the pathogenesis of pituitary neoplasia. Clonal analysis allows one to make the important distinction between a polyclonal proliferation in response to a stimulatory factor versus a monoclonal expansion of a genetically aberrant cell. We investigated the clonal origin of pituitary tumors using X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase and hypoxanthine phosphoribosyl-transferase genes. Restriction enzymes were used to distinguish maternal and paternal X-chromosomes, and combined with a methylation-sensitive restriction enzyme to analyze allelic X-inactivation patterns in six pituitary adenomas. All six tumors showed a monoclonal pattern of X-inactivation. These data indicate that nonfunctioning pituitary adenomas are unicellular in origin, a result consistent with the hypothesis that this tumor type is due to somatic mutation.
authors.affiliation: Division of Medicine, Massachusetts General Hospital, Boston 02114.
authors.forename: J M
authors.initials: JM
authors.lastname: Alexander
authors.forename: B M
authors.initials: BM
authors.lastname: Biller
authors.forename: H
authors.initials: H
authors.lastname: Bikkal
authors.forename: N T
authors.initials: NT
authors.lastname: Zervas
authors.forename: A
authors.initials: A
authors.lastname: Arnold
authors.forename: A
authors.initials: A
authors.lastname: Klibanski
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D015139:Blotting, Southern; D002999:Clone Cells; D004303:Dosage Compensation, Genetic; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008745:Methylation; D008875:Middle Aged; D010735:Phosphoglycerate Kinase / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics / Q000473:pathology*; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase