An integrated genomic analysis of human glioblastoma multiforme

D. Williams Parsons, Siân Jones, Xiaosong Zhang, Jimmy Cheng Ho Lin, Rebecca J. Leary, Philipp Angenendt, Parminder Mankoo, Hannah Carter, I. Mei Siu, Gary L Gallia, Alessandro Olivi, Roger McLendon, B. Ahmed Rasheed, Stephen Keir, Tatiana Nikolskaya, Yuri Nikolsky, Dana A. Busam, Hanna Tekleab, Luis A. Diaz, James Hartigan & 13 others Doug R. Smith, Robert L. Strausberg, Suely Kazue Nagahashi Marie, Sueli Mieko Oba Shinjo, Hai Yan, Gregory J Riggins, Darell D. Bigner, Rachel Karchin, Nickolas Papadopoulos, Giovanni Parmigiani, Bert Vogelstein, Victor E Velculescu, Kenneth W Kinzler

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1807-1812
Number of pages6
JournalScience
Volume321
Issue number5897
DOIs
StatePublished - Sep 26 2008

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Glioblastoma
Isocitrate Dehydrogenase
Brain Neoplasms
Mutation
Oligonucleotide Array Sequence Analysis
Catalytic Domain
Technology
Gene Expression
Survival
Genes
Neoplasms
Proteins
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Parsons, D. W., Jones, S., Zhang, X., Lin, J. C. H., Leary, R. J., Angenendt, P., ... Kinzler, K. W. (2008). An integrated genomic analysis of human glioblastoma multiforme. Science, 321(5897), 1807-1812. https://doi.org/10.1126/science.1164382

An integrated genomic analysis of human glioblastoma multiforme. / Parsons, D. Williams; Jones, Siân; Zhang, Xiaosong; Lin, Jimmy Cheng Ho; Leary, Rebecca J.; Angenendt, Philipp; Mankoo, Parminder; Carter, Hannah; Siu, I. Mei; Gallia, Gary L; Olivi, Alessandro; McLendon, Roger; Rasheed, B. Ahmed; Keir, Stephen; Nikolskaya, Tatiana; Nikolsky, Yuri; Busam, Dana A.; Tekleab, Hanna; Diaz, Luis A.; Hartigan, James; Smith, Doug R.; Strausberg, Robert L.; Marie, Suely Kazue Nagahashi; Shinjo, Sueli Mieko Oba; Yan, Hai; Riggins, Gregory J; Bigner, Darell D.; Karchin, Rachel; Papadopoulos, Nickolas; Parmigiani, Giovanni; Vogelstein, Bert; Velculescu, Victor E; Kinzler, Kenneth W.

In: Science, Vol. 321, No. 5897, 26.09.2008, p. 1807-1812.

Research output: Contribution to journalArticle

Parsons, DW, Jones, S, Zhang, X, Lin, JCH, Leary, RJ, Angenendt, P, Mankoo, P, Carter, H, Siu, IM, Gallia, GL, Olivi, A, McLendon, R, Rasheed, BA, Keir, S, Nikolskaya, T, Nikolsky, Y, Busam, DA, Tekleab, H, Diaz, LA, Hartigan, J, Smith, DR, Strausberg, RL, Marie, SKN, Shinjo, SMO, Yan, H, Riggins, GJ, Bigner, DD, Karchin, R, Papadopoulos, N, Parmigiani, G, Vogelstein, B, Velculescu, VE & Kinzler, KW 2008, 'An integrated genomic analysis of human glioblastoma multiforme', Science, vol. 321, no. 5897, pp. 1807-1812. https://doi.org/10.1126/science.1164382
Parsons DW, Jones S, Zhang X, Lin JCH, Leary RJ, Angenendt P et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008 Sep 26;321(5897):1807-1812. https://doi.org/10.1126/science.1164382
Parsons, D. Williams ; Jones, Siân ; Zhang, Xiaosong ; Lin, Jimmy Cheng Ho ; Leary, Rebecca J. ; Angenendt, Philipp ; Mankoo, Parminder ; Carter, Hannah ; Siu, I. Mei ; Gallia, Gary L ; Olivi, Alessandro ; McLendon, Roger ; Rasheed, B. Ahmed ; Keir, Stephen ; Nikolskaya, Tatiana ; Nikolsky, Yuri ; Busam, Dana A. ; Tekleab, Hanna ; Diaz, Luis A. ; Hartigan, James ; Smith, Doug R. ; Strausberg, Robert L. ; Marie, Suely Kazue Nagahashi ; Shinjo, Sueli Mieko Oba ; Yan, Hai ; Riggins, Gregory J ; Bigner, Darell D. ; Karchin, Rachel ; Papadopoulos, Nickolas ; Parmigiani, Giovanni ; Vogelstein, Bert ; Velculescu, Victor E ; Kinzler, Kenneth W. / An integrated genomic analysis of human glioblastoma multiforme. In: Science. 2008 ; Vol. 321, No. 5897. pp. 1807-1812.
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