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

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• 作者：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 ; Kat
• 刊名：Cancer Cell
• 出版年：2010
• 出版时间：18 May 2010
• 年：2010
• 卷：17
• 期：5
• 页码：510-522
• 全文大小：2031 K

文摘

Summary

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.