An integrated genomic analysis of human glioblastoma multiforme.
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.
Parsons
D Williams
DW
Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
Jones
Siân
S
Zhang
Xiaosong
X
Lin
Jimmy Cheng-Ho
JC
Leary
Rebecca J
RJ
Angenendt
Philipp
P
Mankoo
Parminder
P
Carter
Hannah
H
Siu
I-Mei
IM
Gallia
Gary L
GL
Olivi
Alessandro
A
McLendon
Roger
R
Rasheed
B Ahmed
BA
Keir
Stephen
S
Nikolskaya
Tatiana
T
Nikolsky
Yuri
Y
Busam
Dana A
DA
Tekleab
Hanna
H
Diaz
Luis A
LA
Hartigan
James
J
Smith
Doug R
DR
Strausberg
Robert L
RL
Marie
Suely Kazue Nagahashi
SK
Shinjo
Sueli Mieko Oba
SM
Yan
Hai
H
Riggins
Gregory J
GJ
Bigner
Darell D
DD
Karchin
Rachel
R
Papadopoulos
Nick
N
Parmigiani
Giovanni
G
Vogelstein
Bert
B
Velculescu
Victor E
VE
Kinzler
Kenneth W
KW
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
D007521:Isocitrate Dehydrogenase
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