Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma.
Houtan Noushmehr
(1)
,
Daniel Weisenberger
(1)
,
Kristin Diefes
(2)
,
Heidi Phillips
(3)
,
Kanan Pujara
(3)
,
Benjamin Berman
(1)
,
Fei Pan
(1)
,
Christopher Pelloski
(2)
,
Erik Sulman
(2)
,
Krishna Bhat
(2)
,
Roel G.W. Verhaak
(4)
,
Katherine Hoadley
(5)
,
D. Neil Hayes
(5)
,
Charles Perou
(5)
,
Heather Schmidt
(6)
,
Li Ding
(6)
,
Richard Wilson
(6)
,
David van den Berg
(1)
,
Hui Shen
(1)
,
Henrik Bengtsson
(7)
,
Pierre Neuvial
(7)
,
Leslie Cope
(8)
,
Jonathan Buckley
(1)
,
James Herman
(8)
,
Stephen Baylin
(8)
,
Peter Laird
(1)
,
Kenneth Aldape
(2)
1
USC -
University of Southern California
2 The University of Texas M.D. Anderson Cancer Center [Houston]
3 Genentech, Inc.
4 Dana-Farber Cancer Institute [Boston]
5 UNC - University of North Carolina at Chapel Hill [NC, USA]
6 Washington University School of Medicine [Saint Louis, MO]
7 Department of Statistics [Berkeley]
8 Johns Hopkins University School of Medicine [Baltimore]
2 The University of Texas M.D. Anderson Cancer Center [Houston]
3 Genentech, Inc.
4 Dana-Farber Cancer Institute [Boston]
5 UNC - University of North Carolina at Chapel Hill [NC, USA]
6 Washington University School of Medicine [Saint Louis, MO]
7 Department of Statistics [Berkeley]
8 Johns Hopkins University School of Medicine [Baltimore]
Houtan Noushmehr
- Fonction : Auteur
- PersonId : 775000
- ORCID : 0000-0003-4051-8114
Fei Pan
- Fonction : Auteur
- PersonId : 775001
- ORCID : 0000-0002-6871-4902
Pierre Neuvial
- Fonction : Auteur
- PersonId : 11
- IdHAL : pierre-neuvial
- ORCID : 0000-0003-3584-9998
Résumé
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.