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- Title
DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.
- Authors
Zheng, Shichun; Houseman, E Andres; Morrison, Zachary; Wrensch, Margaret R; Patoka, Joseph S; Ramos, Christian; Haas-Kogan, Daphne A; McBride, Sean; Marsit, Carmen J; Christensen, Brock C; Nelson, Heather H; Stokoe, David; Wiemels, Joseph L; Chang, Susan M; Prados, Michael D; Tihan, Tarik; Vandenberg, Scott R; Kelsey, Karl T; Berger, Mitchel S; Wiencke, John K
- Abstract
We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and III, 52 primary glioblastoma multiforme (GBM), 11 secondary GBM, 54 oligodendroglioma/oligoastrocytoma II and III) and 13 nonmalignant brain tissues for aberrant methylation with quantitative methylation-specific PCR (qMS-PCR) and for EZH2 and IGFBP2 expression with quantitative reverse transcription PCR (qRT-PCR). Global methylation was assessed by measuring long interspersed nuclear element-1 (LINE1) methylation. Unsupervised clustering analyses yielded 3 methylation patterns (classes). Class 1 (MGMT, PTEN, RASSF1A, TMS1, ZNF342, EMP3, SOCS1, RFX1) was highly methylated in 82% (75/91) of lower-grade astrocytic and oligodendroglial tumors, 73% (8/11) of secondary GBMs, and 12% (6/52) of primary GBMs. The primary GBMs in this class were early onset (median age 37 years). Class 2 (HOXA9 and SLIT2) was highly methylated in 37% (19/52) of primary GBMs. None of the 10 genes for class 3 that were differentially methylated in classes 1 and 2 were hypermethylated in 92% (12/13) of nonmalignant brain tissues and 52% (27/52) of primary GBMs. Class 1 tumors had elevated EZH2 expression but not elevated IGFBP2; class 2 tumors had both high IGFBP2 and high EZH2 expressions. The gene-specific hypermethylation class correlated with higher levels of global LINE1 methylation and longer patient survival times. These findings indicate a generalized hypermethylation phenotype in glioma linked to improved survival and low IGFBP2. DNA methylation markers are useful in characterizing distinct glioma subtypes and may hold promise for clinical applications.
- Publication
Neuro-oncology, 2011, Vol 13, Issue 3, p280
- ISSN
1523-5866
- Publication type
Journal Article
- DOI
10.1093/neuonc/noq190