An integrated genomic analysis of human glioblastoma Multiforme

被引：4538

作者：

Parsons, D. Williams ^{[1
,2
,3
]}

Jones, Sian ^{[1
,2
]}

Zhang, Xiaosong ^{[1
,2
]}

Lin, Jimmy Cheng-Ho ^{[1
,2
]}

Leary, Rebecca J. ^{[1
,2
]}

Angenendt, Philipp ^{[1
,2
]}

Mankoo, Parminder ^{[4
]}

Carter, Hannah ^{[4
]}

Siu, I-Mei ^{[5
]}

Gallia, Gary L. ^{[5
]}

Olivi, Alessandro ^{[5
]}

McLendon, Roger ^{[6
,7
]}

Rasheed, B. Ahmed ^{[6
,7
]}

Keir, Stephen ^{[6
,7
]}

Nikolskaya, Tatiana ^{[8
]}

Nikolsky, Yuri ^{[9
]}

Busam, Dana A. ^{[10
]}

Tekleab, Hanna ^{[10
]}

Diaz, Luis A., Jr. ^{[1
,2
]}

Hartigan, James ^{[11
]}

Smith, Doug R. ^{[11
]}

Strausberg, Robert L. ^{[10
]}

Marie, Suely Kazue Nagahashi ^{[12
]}

Shinjo, Sueli Mieko Oba ^{[12
]}

Yan, Hai ^{[6
,7
]}

Riggins, Gregory J. ^{[5
]}

Bigner, Darell D. ^{[6
,7
]}

Karchin, Rachel ^{[4
]}

Papadopoulos, Nick ^{[1
,2
]}

Parmigiani, Giovanni ^{[1
,2
]}

Vogelstein, Bert ^{[1
,2
]}

Velculescu, Victor E. ^{[1
,2
]}

Kinzler, Kenneth W. ^{[1
,2
]}

机构：

[1] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA

[2] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA

[3] Baylor Coll Med, Dept Pediat, Hematol Oncol Sect, Houston, TX 77030 USA

[4] Johns Hopkins Med Inst, Dept Biomed Engn, Inst Computat Med, Baltimore, MD 21218 USA

[5] Johns Hopkins Med Inst, Dept Neurosurg, Baltimore, MD 21231 USA

[6] Duke Univ, Med Ctr, Dept Pathol, Pediat Brain Tumor Fdn, Durham, NC 27710 USA

[7] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA

[8] Vavilov Inst Gen Genet, Moscow 117809, Russia

[9] GeneGo Inc, St Joseph, MI 49085 USA

[10] J Craig Venter Inst, Rockville, MD 20850 USA

[11] Agencourt Biosci Corp, Beverly, MA 01915 USA

[12] Univ Sao Paulo, Sch Med, Dept Neurol, Sao Paulo, Brazil

来源：

SCIENCE | 2008年 / 321卷 / 5897期

关键词：

D O I：

10.1126/science.1164382

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1807 / 1812

页数：6

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