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