Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma

被引：1850

作者：

Noushmehr, Houtan ^{[1
]}

Weisenberger, Daniel J. ^{[1
]}

Diefes, Kristin ^{[2
]}

Phillips, Heidi S. ^{[3
]}

Pujara, Kanan ^{[3
]}

Berman, Benjamin P. ^{[1
]}

Pan, Fei ^{[1
]}

Pelloski, Christopher E. ^{[4
]}

Sulman, Erik P. ^{[4
]}

Bhat, Krishna P. ^{[2
]}

Verhaak, Roel G. W. ^{[5
,6
,7
]}

Hoadley, Katherine A. ^{[8
,9
]}

Hayes, D. Neil ^{[8
,9
]}

Perou, Charles M. ^{[8
,9
]}

Schmidt, Heather K. ^{[10
]}

Ding, Li ^{[10
]}

Wilson, Richard K. ^{[10
]}

Van Den Berg, David ^{[1
]}

Shen, Hui ^{[1
]}

Bengtsson, Henrik ^{[11
]}

Neuvial, Pierre ^{[11
]}

Cope, Leslie M. ^{[12
]}

Buckley, Jonathan ^{[1
,13
]}

Herman, James G. ^{[12
]}

Baylin, Stephen B. ^{[12
]}

Laird, Peter W. ^{[1
]}

Aldape, Kenneth ^{[2
]}

机构：

[1] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90033 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[3] Genentech Inc, Dept Tumor Biol & Angiogenesis, San Francisco, CA 94080 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[5] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA

[6] Harvard Univ, Cambridge, MA 02142 USA

[7] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[8] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[9] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[10] Washington Univ, Sch Med, Genome Ctr, Dept Genet, St Louis, MO 63108 USA

[11] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[12] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21231 USA

[13] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

来源：

CANCER CELL | 2010年 / 17卷 / 05期

关键词：

INTEGRATED GENOMIC ANALYSIS; CODON; 132; MUTATION; HIGH-GRADE GLIOMA; DNA METHYLATION; GLIOBLASTOMA-MULTIFORME; PROSTATE-CANCER; RETINOIC ACID; COLORECTAL-CANCER; PROMOTER HYPERMETHYLATION; PROFILING REVEALS;

D O I：

10.1016/j.ccr.2010.03.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We have profiled promoter DNA methylation alterations in 272 glioblastoma tumors in the context of The Cancer Genome Atlas (TCGA). We found that a distinct subset of samples displays concerted hypermethylation at a large number of loci, indicating the existence of a glioma-CpG island methylator phenotype (G-CIMP). We validated G-CIMP in a set of non-TCGA glioblastomas and low-grade gliomas. G-CIMP tumors belong to the proneural subgroup, are more prevalent among lower-grade gliomas, display distinct copy-number alterations, and are tightly associated with IDH1 somatic mutations. Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds.

引用

页码：510 / 522

页数：13

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