Evidence map›Paper›PMID 30446899›Full record

ArticleJournal of neuro-oncology2019

Functional relevance of genes predicted to be affected by epigenetic alterations in atypical teratoid/rhabdoid tumors.

Isabel Tegeder, Katharina Thiel, Serap Erkek, Pascal D Johann, Johannes Berlandi, Venu Thatikonda, Michael C Frühwald, Marcel Kool, Astrid Jeibmann, Martin Hasselblatt

Abstract read
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In one paragraph

Article in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Multifaceted Role of PRDM Proteins in Human Cancer.International journal of molecular sciences · 2020
    Review
  8. Article
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

10 authors at 3 institutions in 1 country.

Isabel TegederInstitute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany.
Katharina ThielInstitute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany.
Serap ErkekHopp-Children's Cancer Center at the NCT Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Pascal D JohannHopp-Children's Cancer Center at the NCT Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Johannes BerlandiInstitute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany.
Venu ThatikondaHopp-Children's Cancer Center at the NCT Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Michael C FrühwaldChildren's Hospital Augsburg, Swabian Children's Cancer Center, Stenglinstr. 2, 86156, Augsburg, Germany.
Marcel KoolHopp-Children's Cancer Center at the NCT Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Astrid JeibmannInstitute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany.
Martin HasselblattInstitute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany. hasselblatt@uni-muenster.de.ORCID http://orcid.org/0000-0003-2707-8484
University Hospital Münster · DEGerman Cancer Research Center · DEUniversity Hospital Augsburg · DE

Funding

Deutsche Forschungsgemeinschaft HA3060/5-1IZKF Ha3/019/15
6 · The paper itself

Abstract

purposeAtypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly arising in infants. Mutations of SWI/SNF chromatin remodeling complex members SMARCB1/INI1 or (rarely) SMARCA4/Brg1 are the sole recurrent genetic lesions. Epigenetic studies revealed a large number of genes predicted to be affected by differential histone modifications in ATRT, but the role of these genes in the biology of ATRT remains uncertain. We therefore aimed at exploring the role of these genes in the detrimental effects of SMARCB1-deficiency.

methodsThe functional relevance of 1083 genes predicted to be affected by epigenetic alterations in ATRT was examined in vivo using a Drosophila melanogaster model of SMARCB1-deficiency. Human orthologues of genes whose knockdown modified the phenotype in the Gal4-UAS fly model were further examined in ATRT samples and SMARCB1-deficient rhabdoid tumor cells.

resultsKnockdown of Snr1, the fly orthologue of SMARCB1, resulted in a lethal phenotype and epigenetic alterations in the fly model. The lethal phenotype was shifted to later stages of development upon additional siRNA knockdown of 89 of 1083 genes screened in vivo. These included TGF-beta receptor signaling pathway related genes, e.g. CG10348, the fly orthologue of transcriptional regulator PRDM16. Subsequently, PRDM16 was found to be over-expressed in ATRT samples and knockdown of PRDM16 in SMARCB1-deficient rhabdoid tumor cells reduced proliferation.

conclusionsThese results suggest that a subset of genes affected by differential histone modification in ATRT is involved in the detrimental effects of SMARCB1-deficiency and also relevant in the biology of ATRT.

Indexed as

Epigenesis, GeneticAnimalsBrain NeoplasmsCell Line, TumorDNA-Binding ProteinsDrosophila melanogasterDrosophila ProteinsHistonesHumansRhabdoid TumorSMARCB1 ProteinTeratomaTranscription FactorsDNA-Binding ProteinsDrosophila ProteinsHistonesPRDM16 protein, humanSMARCB1 ProteinSMARCB1 protein, humanSnr1 protein, DrosophilaTranscription FactorsDrosophila melanogasterHistone modificationsMalignant rhabdoid tumorPRDM16SMARCB1TGFbeta signaling

Identifiers

PMID30446899
OpenAlexW2901433206

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.