title: An integrated genomic analysis of human glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleotide arrays, and performed gene expression analyses using next-generation sequencing technologies in 22 human tumor samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs. Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs.
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
authors.forename: Siân
authors.initials: S
authors.lastname: Jones
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Zhang
authors.forename: Jimmy Cheng-Ho
authors.initials: JC
authors.lastname: Lin
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Leary
authors.forename: Philipp
authors.initials: P
authors.lastname: Angenendt
authors.forename: Parminder
authors.initials: P
authors.lastname: Mankoo
authors.forename: Hannah
authors.initials: H
authors.lastname: Carter
authors.forename: I-Mei
authors.initials: IM
authors.lastname: Siu
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Olivi
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
authors.forename: B Ahmed
authors.initials: BA
authors.lastname: Rasheed
authors.forename: Stephen
authors.initials: S
authors.lastname: Keir
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nikolskaya
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.forename: Dana A
authors.initials: DA
authors.lastname: Busam
authors.forename: Hanna
authors.initials: H
authors.lastname: Tekleab
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: James
authors.initials: J
authors.lastname: Hartigan
authors.forename: Doug R
authors.initials: DR
authors.lastname: Smith
authors.forename: Robert L
authors.initials: RL
authors.lastname: Strausberg
authors.forename: Suely Kazue Nagahashi
authors.initials: SK
authors.lastname: Marie
authors.forename: Sueli Mieko Oba
authors.initials: SM
authors.lastname: Shinjo
authors.forename: Hai
authors.initials: H
authors.lastname: Yan
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Rachel
authors.initials: R
authors.lastname: Karchin
authors.forename: Nick
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: D007521:Isocitrate Dehydrogenase
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