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Genome-wide methylation analyses in glioblastoma multiforme.

Publication ,  Journal Article
Lai, RK; Chen, Y; Guan, X; Nousome, D; Sharma, C; Canoll, P; Bruce, J; Sloan, AE; Cortes, E; Vonsattel, J-P; Su, T; Delgado-Cruzata, L ...
Published in: PLoS One
2014

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery and validation datasets. Global methylation levels were assessed by analysis of L1 retrotransposon (LINE1), 5 methyl-deoxycytidine (5m-dC) and 5 hydroxylmethyl-deoxycytidine (5hm-dC) in the discovery dataset. We validated a total of 1548 CpG sites (1307 genes) that were differentially methylated in GBM compared to controls. There were more than twice as many hypomethylated genes as hypermethylated ones. Both the discovery and validation datasets found 5 tumor methylation classes. Pathway analyses showed that the top ten pathways in hypomethylated genes were all related to functions of innate and acquired immunities. Among hypermethylated pathways, transcriptional regulatory network in embryonic stem cells was the most significant. In the study of global methylation markers, 5m-dC level was the best discriminant among methylation classes, whereas in survival analyses, high level of LINE1 methylation was an independent, favorable prognostic factor in the discovery dataset. Based on a pathway approach, hypermethylation in genes that control stem cell differentiation were significant, poor prognostic factors of overall survival in both the discovery and validation datasets. Approaches that targeted these methylated genes may be a future therapeutic goal.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

2

Start / End Page

e89376

Location

United States

Related Subject Headings

  • Promoter Regions, Genetic
  • Middle Aged
  • Male
  • Humans
  • Glioblastoma
  • Genome-Wide Association Study
  • General Science & Technology
  • Female
  • DNA Methylation
  • CpG Islands
 

Citation

APA
Chicago
ICMJE
MLA
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Lai, R. K., Chen, Y., Guan, X., Nousome, D., Sharma, C., Canoll, P., … Barnholtz-Sloan, J. (2014). Genome-wide methylation analyses in glioblastoma multiforme. PLoS One, 9(2), e89376. https://doi.org/10.1371/journal.pone.0089376
Lai, Rose K., Yanwen Chen, Xiaowei Guan, Darryl Nousome, Charu Sharma, Peter Canoll, Jeffrey Bruce, et al. “Genome-wide methylation analyses in glioblastoma multiforme.PLoS One 9, no. 2 (2014): e89376. https://doi.org/10.1371/journal.pone.0089376.
Lai RK, Chen Y, Guan X, Nousome D, Sharma C, Canoll P, et al. Genome-wide methylation analyses in glioblastoma multiforme. PLoS One. 2014;9(2):e89376.
Lai, Rose K., et al. “Genome-wide methylation analyses in glioblastoma multiforme.PLoS One, vol. 9, no. 2, 2014, p. e89376. Pubmed, doi:10.1371/journal.pone.0089376.
Lai RK, Chen Y, Guan X, Nousome D, Sharma C, Canoll P, Bruce J, Sloan AE, Cortes E, Vonsattel J-P, Su T, Delgado-Cruzata L, Gurvich I, Santella RM, Ostrom Q, Lee A, Gregersen P, Barnholtz-Sloan J. Genome-wide methylation analyses in glioblastoma multiforme. PLoS One. 2014;9(2):e89376.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

2

Start / End Page

e89376

Location

United States

Related Subject Headings

  • Promoter Regions, Genetic
  • Middle Aged
  • Male
  • Humans
  • Glioblastoma
  • Genome-Wide Association Study
  • General Science & Technology
  • Female
  • DNA Methylation
  • CpG Islands