Evidence map›Paper›PMID 28444909›Full record

ArticleThe Journal of pathology2017

The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type.

Yemin Wang, Shary Yuting Chen, Anthony N Karnezis, Shane Colborne, Nancy Dos Santos, Jessica D Lang, William Pd Hendricks, Krystal A Orlando, Damian Yap, Friedrich Kommoss and 5 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% 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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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  18. Heterogeneity and treatment landscape of ovarian carcinoma.Nature reviews. Clinical oncology · 2023
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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

15 authors at 4 institutions in 2 countries.

Yemin WangDepartment of Pathology and Laboratory Medicine, University of British Columbia and Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.ORCID 0000-0002-2970-9510
Shary Yuting ChenDepartment of Pathology and Laboratory Medicine, University of British Columbia and Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Anthony N KarnezisDepartment of Pathology and Laboratory Medicine, University of British Columbia and Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Shane ColborneMichael Smith Genome Science Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
Nancy Dos SantosDepartment of Experimental Therapeutics, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Jessica D LangDivision of Integrated Cancer Genomics, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.
William Pd HendricksDivision of Integrated Cancer Genomics, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.
Krystal A OrlandoDepartment of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Damian YapDepartment of Pathology and Laboratory Medicine, University of British Columbia and Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Friedrich KommossDepartment of Pathology and Laboratory Medicine, University of British Columbia and Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Marcel B BallyDepartment of Experimental Therapeutics, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Gregg B MorinDepartment of Experimental Therapeutics, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Jeffrey M TrentDivision of Integrated Cancer Genomics, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.
Bernard E WeissmanDepartment of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
David G HuntsmanDepartment of Pathology and Laboratory Medicine, University of British Columbia and Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
BC Cancer Agency · CATranslational Genomics Research Institute · USUniversity of North Carolina at Chapel Hill · USCanada's Michael Smith Genome Sciences Centre · CA

Funding

The Tumor Suppressor Role of SMARCA4 in SCCOHTR01CA195670 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HUNTSMAN, DAVID, TRENT, JEFFREY M. · 2015 to 2019
$3.7M
NCI NIH HHS R01 CA195670
6 · The paper itself

Abstract

Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodelling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of the SWI/SNF chromatin-remodelling complex in transcriptional control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for oncogenic transformation. Herein, we report that approximately 80% (19/24) of SCCOHT tumour samples have strong expression of the histone methyltransferase EZH2 by immunohistochemistry, with the rest expressing variable amounts of EZH2. Re-expression of SMARCA4 suppressed the expression of EZH2 in SCCOHT cells. In comparison to other ovarian cell lines, SCCOHT cells displayed hypersensitivity to EZH2 shRNAs and two selective EZH2 inhibitors, GSK126 and EPZ-6438. EZH2 inhibitors induced cell cycle arrest, apoptosis, and cell differentiation in SCCOHT cells, along with the induction of genes involved in cell cycle regulation, apoptosis, and neuron-like differentiation. EZH2 inhibitors suppressed tumour growth and improved the survival of mice bearing SCCOHT xenografts. Therefore, our data suggest that loss of SMARCA4 creates a dependency on the catalytic activity of EZH2 in SCCOHT cells and that pharmacological inhibition of EZH2 is a promising therapeutic strategy for treating this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Indexed as

AnimalsApoptosisCarcinoma, Ovarian EpithelialCarcinoma, Small CellCell Cycle CheckpointsCell Line, TumorCell Transformation, NeoplasticDNA HelicasesDown-RegulationEnhancer of Zeste Homolog 2 ProteinFemaleHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHumansHypercalcemiaNeoplasms, Glandular and EpithelialDNA HelicasesEnhancer of Zeste Homolog 2 ProteinEzh2 protein, mouseHistone-Lysine N-MethyltransferaseHistone MethyltransferasesNuclear ProteinsSMARCA4 protein, humanTranscription Factorschromatin remodelling complexdifferentiationEZH2ovarian cancerSCCOHTSMARCA4SWI/SNF

Identifiers

PMID28444909
PMCPMC6857704
OpenAlexW2607808741

What OpenQuestion holds

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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.