Document Detail


DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.
MedLine Citation:
PMID:  21339190     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Neuro-oncology     Volume:  13     ISSN:  1523-5866     ISO Abbreviation:  Neuro-oncology     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-22     Completed Date:  2011-06-14     Revised Date:  2013-07-19    
Medline Journal Info:
Nlm Unique ID:  100887420     Medline TA:  Neuro Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  280-9     Citation Subset:  IM    
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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MeSH Terms
Descriptor/Qualifier:
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
Polycomb Repressive Complex 2
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:
CA126831/CA/NCI NIH HHS; ES06717/ES/NIEHS NIH HHS; P50 CA097257/CA/NCI NIH HHS; P50CA0927257/CA/NCI NIH HHS; R01 CA052689-22/CA/NCI NIH HHS; R01 CA126831/CA/NCI NIH HHS; R01 ES006717/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 0/DNA-Binding Proteins; 0/Insulin-Like Growth Factor Binding Protein 2; 0/RNA, Messenger; 0/Transcription Factors; 0/Tumor Suppressor Proteins; EC 2.1.1.43/EZH2 protein, human; EC 2.1.1.43/Polycomb Repressive Complex 2; 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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