An epigenetic biomarker panel for glioblastoma multiforme personalized medicine through DNA methylation analysis of human embryonic stem cell-like signature

Jung-Hsien Chiang, Wan Shu Cheng, Leroy Hood, Qiang Tian

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Alterations of DNA methylation occur during the course of both stem cell development and tumorigenesis. We present a novel strategy that can be used to stratify glioblastoma multiforme (GBM) patients through the epigenetic states of genes associated with human embryonic stem cell (hESC) identity in order to 1) assess linkages between the methylation signatures of these stem cell genes and survival of GBM patients, and 2) delineate putative mechanisms leading to poor prognosis in some patient subgroups. A DNA methylation signature was established for stratifying GBM patients into several hESC methylator subgroups. The hESC methylator-negative phenotype has demonstrated poor survival and upregulation of glioma stem cell (GSC) markers, and is enriched in one of the previously defined transcriptomic phenotypes - the mesenchymal phenotype. We further identified a refined signature of 36 genes as the gene panel, including SOX2, POU3F2, FGFR2, GAP43, NTRK2, NTRK3, and NKX2-2, which are highly enriched in the nervous system. Both signatures outperformed the O6-methylguanine-DNA methyltransferase (MGMT) methylation test in predicting patient's outcome. These findings were also validated through an independent dataset of patients. Furthermore, through statistical analyses, both signatures were examined significantly. Hypomethylation of hESC-associated genes predicted poorer clinical outcome in GBM, supporting the idea that epigenetic activation of stem cell genes contributes to GBM aggression. The gene panel presented herein may be developed into clinical assays for patient stratification and future personalized medicine interventions.

Original languageEnglish
Pages (from-to)310-323
Number of pages14
JournalOMICS A Journal of Integrative Biology
Volume18
Issue number5
DOIs
Publication statusPublished - 2014 May 1

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Precision Medicine
Biomarkers
DNA Methylation
Glioblastoma
Stem cells
Epigenomics
Medicine
Genes
Stem Cells
Phenotype
Methyltransferases
Methylation
Human Embryonic Stem Cells
Aggression
Glioma
Neurology
Nervous System
Cell Survival
Carcinogenesis
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

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abstract = "Alterations of DNA methylation occur during the course of both stem cell development and tumorigenesis. We present a novel strategy that can be used to stratify glioblastoma multiforme (GBM) patients through the epigenetic states of genes associated with human embryonic stem cell (hESC) identity in order to 1) assess linkages between the methylation signatures of these stem cell genes and survival of GBM patients, and 2) delineate putative mechanisms leading to poor prognosis in some patient subgroups. A DNA methylation signature was established for stratifying GBM patients into several hESC methylator subgroups. The hESC methylator-negative phenotype has demonstrated poor survival and upregulation of glioma stem cell (GSC) markers, and is enriched in one of the previously defined transcriptomic phenotypes - the mesenchymal phenotype. We further identified a refined signature of 36 genes as the gene panel, including SOX2, POU3F2, FGFR2, GAP43, NTRK2, NTRK3, and NKX2-2, which are highly enriched in the nervous system. Both signatures outperformed the O6-methylguanine-DNA methyltransferase (MGMT) methylation test in predicting patient's outcome. These findings were also validated through an independent dataset of patients. Furthermore, through statistical analyses, both signatures were examined significantly. Hypomethylation of hESC-associated genes predicted poorer clinical outcome in GBM, supporting the idea that epigenetic activation of stem cell genes contributes to GBM aggression. The gene panel presented herein may be developed into clinical assays for patient stratification and future personalized medicine interventions.",
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An epigenetic biomarker panel for glioblastoma multiforme personalized medicine through DNA methylation analysis of human embryonic stem cell-like signature. / Chiang, Jung-Hsien; Cheng, Wan Shu; Hood, Leroy; Tian, Qiang.

In: OMICS A Journal of Integrative Biology, Vol. 18, No. 5, 01.05.2014, p. 310-323.

Research output: Contribution to journalArticle

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