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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-2-22
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/EZH2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1523-5866
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pubmed:author |
pubmed-author:BergerMitchel SMS,
pubmed-author:ChangSusan MSM,
pubmed-author:ChristensenBrock CBC,
pubmed-author:Haas-KoganDaphne ADA,
pubmed-author:HousemanE AndresEA,
pubmed-author:KelseyKarl TKT,
pubmed-author:MarsitCarmen JCJ,
pubmed-author:McBrideSeanS,
pubmed-author:MorrisonZacharyZ,
pubmed-author:NelsonHeather HHH,
pubmed-author:PatokaJoseph SJS,
pubmed-author:PradosMichael DMD,
pubmed-author:RamosChristianC,
pubmed-author:StokoeDavidD,
pubmed-author:TihanTarikT,
pubmed-author:VandenbergScott RSR,
pubmed-author:WiemelsJoseph LJL,
pubmed-author:WienckeJohn KJK,
pubmed-author:WrenschMargaret RMR,
pubmed-author:ZhengShichunS
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pubmed:issnType |
Electronic
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
280-9
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pubmed:meshHeading |
pubmed-meshheading:21339190-Adolescent,
pubmed-meshheading:21339190-Adult,
pubmed-meshheading:21339190-Brain Neoplasms,
pubmed-meshheading:21339190-DNA, Neoplasm,
pubmed-meshheading:21339190-DNA Methylation,
pubmed-meshheading:21339190-DNA-Binding Proteins,
pubmed-meshheading:21339190-Female,
pubmed-meshheading:21339190-Gene Amplification,
pubmed-meshheading:21339190-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21339190-Glioma,
pubmed-meshheading:21339190-Humans,
pubmed-meshheading:21339190-Insulin-Like Growth Factor Binding Protein 2,
pubmed-meshheading:21339190-Long Interspersed Nucleotide Elements,
pubmed-meshheading:21339190-Male,
pubmed-meshheading:21339190-Middle Aged,
pubmed-meshheading:21339190-Polymerase Chain Reaction,
pubmed-meshheading:21339190-Prognosis,
pubmed-meshheading:21339190-RNA, Messenger,
pubmed-meshheading:21339190-Receptor, Epidermal Growth Factor,
pubmed-meshheading:21339190-Survival Rate,
pubmed-meshheading:21339190-Transcription Factors,
pubmed-meshheading:21339190-Tumor Suppressor Proteins,
pubmed-meshheading:21339190-Young Adult
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pubmed:year |
2011
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pubmed:articleTitle |
DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.
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pubmed:affiliation |
Department of Neurological Surgery, University of California-San Francisco, Helen Diller Family Cancer Center, 1450 3rd Street, San Francisco, CA 94158, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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