Evidence map›Paper›PMID 23034519›Full record

ArticleGenome biology2012

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

Anneleen Decock, Maté Ongenaert, Jasmien Hoebeeck, Katleen De Preter, Gert Van Peer, Wim Van Criekinge, Ruth Ladenstein, Johannes H Schulte, Rosa Noguera, Raymond L Stallings and 6 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 81 citations in OpenAlex.

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  13. Epigenetic Dysregulation inInternational journal of molecular sciences · 2023
    Review
  14. Article
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  16. Article
  17. Article
  18. MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 8 institutions in 5 countries.

Anneleen Decock
Maté Ongenaert
Jasmien Hoebeeck
Katleen De Preter
Gert Van Peer
Wim Van Criekinge
Ruth Ladenstein
Johannes H Schulte
Rosa Noguera
Raymond L Stallings
An Van Damme
Geneviève Laureys
Joëlle Vermeulen
Tom Van Maerken
Frank Speleman
Jo Vandesompele
Ghent University Hospital · BEAntwerp University Hospital · BEEssen University Hospital · DEGhent University · BEHôpital de Jolimont · BENational Children’s Research Centre · IESt Anna Children's Hospital · ATUniversitat de València · ES

Funding

MiRNA Expression in NeuroblastomaR01CA127496 · NCI · ROYAL COLLEGE OF SURGEONS IN IRELAND · PI STALLINGS, RAYMOND LOUIS · 2008 to 2012
$976k
NCI NIH HHS 5R01CA127496
6 · The paper itself

Abstract

backgroundAccurate 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.

resultsTo 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.

conclusionsThis 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.

Indexed as

AzacitidineBiomarkers, TumorCell Line, TumorChromograninsDatabases, GeneticDecitabineDNA MethylationEpigenomicsGene Expression Regulation, NeoplasticGenome, HumanGTP-Binding Protein alpha Subunits, GsHCT116 CellsHigh-Throughput Nucleotide SequencingHumansNeuroblastomaPromoter Regions, GeneticAzacitidineBiomarkers, TumorChromograninsDecitabineGNAS protein, humanGTP-Binding Protein alpha Subunits, Gs

Identifiers

PMID23034519
PMCPMC3491423
OpenAlexW2126882311

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.