| DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression. | |
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MedLine Citation:
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PMID: 21339190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Shichun Zheng; E Andres Houseman; Zachary Morrison; Margaret R Wrensch; Joseph S Patoka; Christian Ramos; Daphne A Haas-Kogan; Sean McBride; Carmen J Marsit; Brock C Christensen; Heather H Nelson; David Stokoe; Joseph L Wiemels; Susan M Chang; Michael D Prados; Tarik Tihan; Scott R Vandenberg; Karl T Kelsey; Mitchel S Berger; John K Wiencke |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Neuro-oncology Volume: 13 ISSN: 1523-5866 ISO Abbreviation: Neuro-oncology Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-22 Completed Date: 2011-06-14 Revised Date: 2012-09-18 |
Medline Journal Info:
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Nlm Unique ID: 100887420 Medline TA: Neuro Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 280-9 Citation Subset: IM |
Affiliation:
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Department of Neurological Surgery, University of California-San Francisco, Helen Diller Family Cancer Center, 1450 3rd Street, San Francisco, CA 94158, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Brain Neoplasms / classification, genetics* DNA Methylation* DNA, Neoplasm / genetics DNA-Binding Proteins / genetics* Female Gene Amplification Gene Expression Regulation, Neoplastic Glioma / classification, genetics* Humans Insulin-Like Growth Factor Binding Protein 2 / genetics* Long Interspersed Nucleotide Elements / genetics Male Middle Aged Polymerase Chain Reaction Prognosis RNA, Messenger / genetics* Receptor, Epidermal Growth Factor / genetics Survival Rate Transcription Factors / genetics* Tumor Suppressor Proteins / genetics Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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CA126831/CA/NCI NIH HHS; ES06717/ES/NIEHS NIH HHS; P50CA0927257/CA/NCI NIH HHS; R01 CA052689-22/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/DNA-Binding Proteins; 0/EZH2 protein, human; 0/Insulin-Like Growth Factor Binding Protein 2; 0/RNA, Messenger; 0/Transcription Factors; 0/Tumor Suppressor Proteins; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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