Evidence map›Paper›PMID 28650485›Full record

ArticleNature genetics2017

Neuroblastoma is composed of two super-enhancer-associated differentiation states.

Tim van Groningen, Jan Koster, Linda J Valentijn, Danny A Zwijnenburg, Nurdan Akogul, Nancy E Hasselt, Marloes Broekmans, Franciska Haneveld, Natalia E Nowakowska, Johannes Bras and 21 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 386 papers.

0numbers the graph read from it
0cells of the map it votes in
386citing papers in PubMed
–field-weighted citation impact
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

386 citing papers in PubMed.

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326 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Tim van GroningenDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Jan KosterDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Linda J ValentijnDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Danny A ZwijnenburgDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Nurdan AkogulDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Nancy E HasseltDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Marloes BroekmansDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Franciska HaneveldDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Natalia E NowakowskaDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Johannes BrasDepartment of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
Carel J M van NoeselDepartment of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
Aldo JongejanDepartment of Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-8948-2549
Antoine H van KampenDepartment of Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-1025-7232
Linda KosterDepartment of Genome Diagnostics, Academic Medical Center, Amsterdam, the Netherlands.
Frank BaasDepartment of Genome Diagnostics, Academic Medical Center, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-3912-5428
Lianne van Dijk-KerkhovenDepartment of Clinical Genetics, VU Medical Center, Amsterdam, the Netherlands.
Margriet Huizer-SmitDepartment of Clinical Genetics, VU Medical Center, Amsterdam, the Netherlands.
Maria C LeccaDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Alvin ChanDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Arjan LakemanDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Piet MolenaarDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Richard VolckmannDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Ellen M WesterhoutDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Mohamed HamdiDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Peter G van SluisDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Marli E EbusDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Jan J MolenaarDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Godelieve A TytgatPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Bart A WestermanDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Johan van NesDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
Rogier VersteegDepartment of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-7172-0388

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroblastoma and other pediatric tumors show a paucity of gene mutations, which has sparked an interest in their epigenetic regulation. Several tumor types include phenotypically divergent cells, resembling cells from different lineage development stages. It has been proposed that super-enhancer-associated transcription factor (TF) networks underlie lineage identity, but the role of these enhancers in intratumoral heterogeneity is unknown. Here we show that most neuroblastomas include two types of tumor cells with divergent gene expression profiles. Undifferentiated mesenchymal cells and committed adrenergic cells can interconvert and resemble cells from different lineage differentiation stages. ChIP-seq analysis of isogenic pairs of mesenchymal and adrenergic cells identified a distinct super-enhancer landscape and super-enhancer-associated TF network for each cell type. Expression of the mesenchymal TF PRRX1 could reprogram the super-enhancer and mRNA landscapes of adrenergic cells toward a mesenchymal state. Mesenchymal cells were more chemoresistant in vitro and were enriched in post-therapy and relapse tumors. Two super-enhancer-associated TF networks, which probably mediate lineage control in normal development, thus dominate epigenetic control of neuroblastoma and shape intratumoral heterogeneity.

Indexed as

Epigenesis, GeneticAC133 AntigenAdrenergic NeuronsCell DifferentiationCell LineageCell Line, TumorHomeodomain ProteinsHumansMesodermNeuroblastomaTranscription FactorsTranscriptomeAC133 AntigenHomeodomain ProteinsPRRX1 protein, humanTranscription Factors

Identifiers

PMID28650485

What OpenQuestion holds

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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.