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

Houtan Noushmehr; Daniel J. Weisenberger; Kristin Diefes; Heidi S. Phillips; Kanan Pujara; Benjamin P. Berman; Fei Pan; Christopher E. Pelloski; Erik P. Sulman; Krishna P. Bhat; Roel G.W. Verhaak; Katherine A. Hoadley; D. Neil Hayes; Charles M. Perou; Heather K. Schmidt; Li Ding; Richard K. Wilson; David Van Den Berg; Hui Shen; Henrik Bengtsson; Pierre Neuvial; Leslie M. Cope; Jonathan Buckley; James G. Herman; Stephen B. Baylin; Peter W. Laird; Kenneth Aldape

doi:10.1016/j.ccr.2010.03.017

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

Houtan Noushmehr
, Daniel J. Weisenberger
, Kristin Diefes
, Heidi S. Phillips
, Kanan Pujara
, Benjamin P. Berman
, Fei Pan
, Christopher E. Pelloski
, Erik P. Sulman
, Krishna P. Bhat
, Roel G.W. Verhaak
, Katherine A. Hoadley
, D. Neil Hayes
, Charles M. Perou
, Heather K. Schmidt
, Li Ding
, Richard K. Wilson
, David Van Den Berg
, Hui Shen
, Henrik Bengtsson

Pierre Neuvial, Leslie M. Cope, Jonathan Buckley, James G. Herman, Stephen B. Baylin, Peter W. Laird^*, Kenneth Aldape

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2040 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	510-522
Number of pages	13
Journal	Cancer Cell
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2010.03.017
State	Published - 18 May 2010
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by NIH/NCI grants U24 CA126561 and U24 CA143882-01 (P.W.L. and S.B.B.), grants from the M.D. Anderson Center for Cancer Epigenetics, the Brain Tumor Funders' Collaborative, the V Foundation, and the Rose Foundation, and SPORE grant P50CA127001 from NIH/NCI (K.A.). We thank Dennis Maglinte and members of the USC Epigenome Center for helpful discussions, Andreana Rivera for technical assistance, and Marisol Guerrero for editorial assistance. P.W.L. is a shareholder, consultant, and scientific advisory board member of Epigenomics, AG, which has a commercial interest in DNA methylation markers. This work was not supported by Epigenomics, AG. K.A. is a consultant and scientific advisory board member for Castle Biosciences, which has a commercial interest in molecular diagnostics. This work was not supported by Castle Biosciences.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CELLCYCLE
DNA
HUMDISEASE

Access to Document

10.1016/j.ccr.2010.03.017

Cite this

Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., Verhaak, R. G. W., Hoadley, K. A., Hayes, D. N., Perou, C. M., Schmidt, H. K., Ding, L., Wilson, R. K., Van Den Berg, D., Shen, H., ... Aldape, K. (2010). Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma. Cancer Cell, 17(5), 510-522. https://doi.org/10.1016/j.ccr.2010.03.017

@article{741df74551614930be19e31b14249bec,

title = "Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma",

abstract = "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.",

keywords = "CELLCYCLE, DNA, HUMDISEASE",

author = "Houtan Noushmehr and Weisenberger, \{Daniel J.\} and Kristin Diefes and Phillips, \{Heidi S.\} and Kanan Pujara and Berman, \{Benjamin P.\} and Fei Pan and Pelloski, \{Christopher E.\} and Sulman, \{Erik P.\} and Bhat, \{Krishna P.\} and Verhaak, \{Roel G.W.\} and Hoadley, \{Katherine A.\} and Hayes, \{D. Neil\} and Perou, \{Charles M.\} and Schmidt, \{Heather K.\} and Li Ding and Wilson, \{Richard K.\} and \{Van Den Berg\}, David and Hui Shen and Henrik Bengtsson and Pierre Neuvial and Cope, \{Leslie M.\} and Jonathan Buckley and Herman, \{James G.\} and Baylin, \{Stephen B.\} and Laird, \{Peter W.\} and Kenneth Aldape",

note = "Funding Information: This work was supported by NIH/NCI grants U24 CA126561 and U24 CA143882-01 (P.W.L. and S.B.B.), grants from the M.D. Anderson Center for Cancer Epigenetics, the Brain Tumor Funders' Collaborative, the V Foundation, and the Rose Foundation, and SPORE grant P50CA127001 from NIH/NCI (K.A.). We thank Dennis Maglinte and members of the USC Epigenome Center for helpful discussions, Andreana Rivera for technical assistance, and Marisol Guerrero for editorial assistance. P.W.L. is a shareholder, consultant, and scientific advisory board member of Epigenomics, AG, which has a commercial interest in DNA methylation markers. This work was not supported by Epigenomics, AG. K.A. is a consultant and scientific advisory board member for Castle Biosciences, which has a commercial interest in molecular diagnostics. This work was not supported by Castle Biosciences. ",

year = "2010",

month = may,

day = "18",

doi = "10.1016/j.ccr.2010.03.017",

language = "אנגלית",

volume = "17",

pages = "510--522",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

}

Noushmehr, H, Weisenberger, DJ, Diefes, K, Phillips, HS, Pujara, K, Berman, BP, Pan, F, Pelloski, CE, Sulman, EP, Bhat, KP, Verhaak, RGW, Hoadley, KA, Hayes, DN, Perou, CM, Schmidt, HK, Ding, L, Wilson, RK, Van Den Berg, D, Shen, H, Bengtsson, H, Neuvial, P, Cope, LM, Buckley, J, Herman, JG, Baylin, SB, Laird, PW & Aldape, K 2010, 'Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma', Cancer Cell, vol. 17, no. 5, pp. 510-522. https://doi.org/10.1016/j.ccr.2010.03.017

TY - JOUR

T1 - Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma

AU - Noushmehr, Houtan

AU - Weisenberger, Daniel J.

AU - Diefes, Kristin

AU - Phillips, Heidi S.

AU - Pujara, Kanan

AU - Berman, Benjamin P.

AU - Pan, Fei

AU - Pelloski, Christopher E.

AU - Sulman, Erik P.

AU - Bhat, Krishna P.

AU - Verhaak, Roel G.W.

AU - Hoadley, Katherine A.

AU - Hayes, D. Neil

AU - Perou, Charles M.

AU - Schmidt, Heather K.

AU - Ding, Li

AU - Wilson, Richard K.

AU - Van Den Berg, David

AU - Shen, Hui

AU - Bengtsson, Henrik

AU - Neuvial, Pierre

AU - Cope, Leslie M.

AU - Buckley, Jonathan

AU - Herman, James G.

AU - Baylin, Stephen B.

AU - Laird, Peter W.

AU - Aldape, Kenneth

N1 - Funding Information: This work was supported by NIH/NCI grants U24 CA126561 and U24 CA143882-01 (P.W.L. and S.B.B.), grants from the M.D. Anderson Center for Cancer Epigenetics, the Brain Tumor Funders' Collaborative, the V Foundation, and the Rose Foundation, and SPORE grant P50CA127001 from NIH/NCI (K.A.). We thank Dennis Maglinte and members of the USC Epigenome Center for helpful discussions, Andreana Rivera for technical assistance, and Marisol Guerrero for editorial assistance. P.W.L. is a shareholder, consultant, and scientific advisory board member of Epigenomics, AG, which has a commercial interest in DNA methylation markers. This work was not supported by Epigenomics, AG. K.A. is a consultant and scientific advisory board member for Castle Biosciences, which has a commercial interest in molecular diagnostics. This work was not supported by Castle Biosciences.

PY - 2010/5/18

Y1 - 2010/5/18

N2 - 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.

AB - 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.

KW - CELLCYCLE

KW - DNA

KW - HUMDISEASE

UR - https://www.scopus.com/pages/publications/77952108366

U2 - 10.1016/j.ccr.2010.03.017

DO - 10.1016/j.ccr.2010.03.017

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 20399149

AN - SCOPUS:77952108366

SN - 1535-6108

VL - 17

SP - 510

EP - 522

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this