TY - JOUR
T1 - An integrated genomic analysis of human glioblastoma multiforme
AU - Parsons, D. Williams
AU - Jones, Siân
AU - Zhang, Xiaosong
AU - Lin, Jimmy Cheng Ho
AU - Leary, Rebecca J.
AU - Angenendt, Philipp
AU - Mankoo, Parminder
AU - Carter, Hannah
AU - Siu, I. Mei
AU - Gallia, Gary L.
AU - Olivi, Alessandro
AU - McLendon, Roger
AU - Rasheed, B. Ahmed
AU - Keir, Stephen
AU - Nikolskaya, Tatiana
AU - Nikolsky, Yuri
AU - Busam, Dana A.
AU - Tekleab, Hanna
AU - Diaz, Luis A.
AU - Hartigan, James
AU - Smith, Doug R.
AU - Strausberg, Robert L.
AU - Marie, Suely Kazue Nagahashi
AU - Shinjo, Sueli Mieko Oba
AU - Yan, Hai
AU - Riggins, Gregory J.
AU - Bigner, Darell D.
AU - Karchin, Rachel
AU - Papadopoulos, Nick
AU - Parmigiani, Giovanni
AU - Vogelstein, Bert
AU - Velculescu, Victor E.
AU - Kinzler, Kenneth W.
PY - 2008/9/26
Y1 - 2008/9/26
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1164382
DO - 10.1126/science.1164382
M3 - Article
C2 - 18772396
AN - SCOPUS:52949127312
SN - 0036-8075
VL - 321
SP - 1807
EP - 1812
JO - Science
JF - Science
IS - 5897
ER -