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DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.

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.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Zheng S,Houseman EA,Morrison Z,Wrensch MR,Patoka JS,Ramos C,Haas-Kogan DA,McBride S,Marsit CJ,Christensen BC,Nelson HH,Stokoe D,Wiemels JL,Chang SM,Prados MD,Tihan T,Vandenberg SR,Kelsey KT,Berger MS,Wiencke JK

doi

10.1093/neuonc/noq190

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

280-9

issue

eissn

1522-8517

issn

1523-5866

pii

noq190

journal_volume

pub_type

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DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.