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Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.

(2012) GENOME BIOLOGY. 13(10).
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Bioinformatics: from nucleotids to networks (N2N)
Abstract
BACKGROUND: Accurate outcome prediction in neuroblastoma, which is necessary to enable the optimal choice of risk-related therapy, remains a challenge. To improve neuroblastoma patient stratification, this study aimed to identify prognostic tumor DNA methylation biomarkers. RESULTS: To identify genes silenced by promoter methylation, we first applied two independent genome-wide methylation screening methodologies to eight neuroblastoma cell lines. Specifically, we used re-expression profiling upon 5-aza-2'-deoxycytidine (DAC) treatment and massively parallel sequencing after capturing with a methyl-CpG-binding domain (MBD-seq). Putative methylation markers were selected from DAC-upregulated genes through a literature search and an upfront methylation-specific PCR on 20 primary neuroblastoma tumors, as well as through MBD- seq in combination with publicly available neuroblastoma tumor gene expression data. This yielded 43 candidate biomarkers that were subsequently tested by high-throughput methylation-specific PCR on an independent cohort of 89 primary neuroblastoma tumors that had been selected for risk classification and survival. Based on this analysis, methylation of KRT19, FAS, PRPH, CNR1, QPCT, HIST1H3C, ACSS3 and GRB10 was found to be associated with at least one of the classical risk factors, namely age, stage or MYCN status. Importantly, HIST1H3C and GNAS methylation was associated with overall and/or event-free survival. CONCLUSIONS: This study combines two genome-wide methylation discovery methodologies and is the most extensive validation study in neuroblastoma performed thus far. We identified several novel prognostic DNA methylation markers and provide a basis for the development of a DNA methylation-based prognostic classifier in neuroblastoma.
Keywords
biomarkers, DNA-methylation, neuroblastoma, epigenetics

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Citation

Please use this url to cite or link to this publication:

Chicago
Decock, Anneleen, Maté Ongenaert, Jasmien Hoebeeck, Katleen De Preter, Gert Van Peer, Wim Van Criekinge, Ruth Ladenstein, et al. 2012. “Genome-wide Promoter Methylation Analysis in Neuroblastoma Identifies Prognostic Methylation Biomarkers.” Genome Biology 13 (10).
APA
Decock, A., Ongenaert, M., Hoebeeck, J., De Preter, K., Van Peer, G., Van Criekinge, W., Ladenstein, R., et al. (2012). Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers. GENOME BIOLOGY, 13(10).
Vancouver
1.
Decock A, Ongenaert M, Hoebeeck J, De Preter K, Van Peer G, Van Criekinge W, et al. Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers. GENOME BIOLOGY. 2012;13(10).
MLA
Decock, Anneleen, Maté Ongenaert, Jasmien Hoebeeck, et al. “Genome-wide Promoter Methylation Analysis in Neuroblastoma Identifies Prognostic Methylation Biomarkers.” GENOME BIOLOGY 13.10 (2012): n. pag. Print.
@article{3097643,
  abstract     = {BACKGROUND: Accurate outcome prediction in neuroblastoma, which is necessary to enable the optimal choice of risk-related therapy, remains a challenge. To improve neuroblastoma patient stratification, this study aimed to identify prognostic tumor DNA methylation biomarkers.
RESULTS: To identify genes silenced by promoter methylation, we first applied two independent genome-wide methylation screening methodologies to eight neuroblastoma cell lines. Specifically, we used re-expression profiling upon 5-aza-2'-deoxycytidine (DAC) treatment and massively parallel sequencing after capturing with a methyl-CpG-binding domain (MBD-seq). Putative methylation markers were selected from DAC-upregulated genes through a literature search and an upfront methylation-specific PCR on 20 primary neuroblastoma tumors, as well as through MBD- seq in combination with publicly available neuroblastoma tumor gene expression data. This yielded 43 candidate biomarkers that were subsequently tested by high-throughput methylation-specific PCR on an independent cohort of 89 primary neuroblastoma tumors that had been selected for risk classification and survival. Based on this analysis, methylation of KRT19, FAS, PRPH, CNR1, QPCT, HIST1H3C, ACSS3 and GRB10 was found to be associated with at least one of the classical risk factors, namely age, stage or MYCN status. Importantly, HIST1H3C and GNAS methylation was associated with overall and/or event-free survival.
CONCLUSIONS: This study combines two genome-wide methylation discovery methodologies and is the most extensive validation study in neuroblastoma performed thus far. We identified several novel prognostic DNA methylation markers and provide a basis for the development of a DNA methylation-based prognostic classifier in neuroblastoma.},
  articleno    = {R95},
  author       = {Decock, Anneleen and Ongenaert, Mat{\'e} and Hoebeeck, Jasmien and De Preter, Katleen and Van Peer, Gert and Van Criekinge, Wim and Ladenstein, Ruth and Schulte, Johannes H and Noguera, Rosa and Stallings, Raymond L and Van Damme, An and Laureys, Genevieve and Vermeulen, Jo{\"e}lle and Van Maerken, Tom and Speleman, Franki and Vandesompele, Jo},
  issn         = {1465-6906},
  journal      = {GENOME BIOLOGY},
  language     = {eng},
  number       = {10},
  pages        = {15},
  title        = {Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.},
  url          = {http://dx.doi.org/10.1186/gb-2012-13-10-r95},
  volume       = {13},
  year         = {2012},
}

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