title: Clonal composition of glioblastoma multiforme.
abstract: Glioblastoma multiforme, the most common and most lethal primary central nervous system neoplasm, is noted for its phenotypic and biological heterogeneity. This heterogeneity may result from genetic alterations accumulated by a single transformed astrocyte as it evolves into a monoclonal tumor. Alternatively, it may be attributed to the presence of multiple biologically and genetically distinct astrocytic populations within a polyclonal tumor. To address the issue of clonal composition of glioblastoma multiforme the authors used two independent approaches: analysis of X-chromosome inactivation and analysis of chromosomes 10 and 17 for tumor-specific somatic deletions. The analysis included 10 tumors from nine female patients with glioblastoma multiforme (eight primary and two recurrent tumors), who were heterozygous at either of two X-chromosome genes (hypoxanthine phosphoribosyl-transferase or phosphoglycerate kinase). Nine glioblastomas multiforme demonstrated a monoclonal pattern on X-chromosome analysis; contamination with normal tissue obscured the analysis in one tumor. Somatic deletions on chromosomes 10 and/or 17 occurred in nine tumors, supporting a monoclonal composition for these tumors. These data suggest that glioblastoma multiforme is a monoclonal neoplasm, derived from the clonal expansion of a single transformed astrocyte that has, as a fundamental step in tumorigenesis, sustained a critical genetic alteration on chromosome 10 and/or 17.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
authors.forename: R A
authors.initials: RA
authors.lastname: Berkman
authors.forename: W C
authors.initials: WC
authors.lastname: Clark
authors.forename: A
authors.initials: A
authors.lastname: Saxena
authors.forename: J T
authors.initials: JT
authors.lastname: Robertson
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
authors.forename: I U
authors.initials: IU
authors.lastname: Ali
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008214:Lymphocytes / Q000502:physiology; D009693:Nucleic Acid Hybridization; D010735:Phosphoglycerate Kinase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase