Evidence map›Paper›PMID 34289358›Full record

ArticleCell reports2021

Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy.

Christopher J Terranova, Ming Tang, Mayinuer Maitituoheti, Ayush T Raman, Archit K Ghosh, Jonathan Schulz, Samir B Amin, Elias Orouji, Katarzyna Tomczak, Sharmistha Sarkar and 16 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  7. Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
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  13. Epithelial-Mesenchymal Transition (EMT) 2021.International journal of molecular sciences · 2022
    Article
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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

26 authors at 6 institutions in 2 countries.

Christopher J TerranovaDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Ming TangDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; FAS informatics, Department of Molecular Biology, Harvard, Cambridge, MA 02138, USA.
Mayinuer MaitituohetiDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Ayush T RamanDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Graduate Program in Quantitative Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Archit K GhoshDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jonathan SchulzDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Samir B AminDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Elias OroujiDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Epigenetics Initiative, Princess Margaret Genomics Centre, Toronto, ON M5G 2C1, Canada.
Katarzyna TomczakDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Sharmistha SarkarDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Junna ObaDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Caitlin CreasyDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Chang-Jiun WuDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Samia KhanDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Rossana LazcanoDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Khalida WaniDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Anand SinghDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Praveen BarrodiaDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Dongyu ZhaoHouston Methodist Academic Institute, Methodist Hospital Research Institute, Houston, TX 77030, USA.
Kaifu ChenDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.
Lauren E HayduSurgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Wei-Lien WangDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Alexander J LazarDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Scott E WoodmanDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Chantale BernatchezDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Kunal RaiDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: krai@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBoston Children's Hospital · USBroad Institute · USJackson Laboratory · USMethodist Hospital · USPrincess Margaret Cancer Centre · CA

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
UCHL5 as a regulator and therapeutic target in metastatic melanomaR01CA245395 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2020 to 2024
$2.0M
Role of KMT2D and aberrant enhancers in modulating tumor microenvironment in melanomaR01CA222214 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2018 to 2022
$1.8M
Epigenetics of Melanoma MetastasisR00CA160578 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2015 to 2017
$747k
Epigenetics of Melanoma MetastasisK99CA160578 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2011 to 2012
$284k
NCI NIH HHS K99 CA160578NCI NIH HHS P30 CA016672NCI NIH HHS R00 CA160578NCI NIH HHS R01 CA222214NCI NIH HHS R01 CA245395
6 · The paper itself

Abstract

The dynamic evolution of chromatin state patterns during metastasis, their relationship with bona fide genetic drivers, and their therapeutic vulnerabilities are not completely understood. Combinatorial chromatin state profiling of 46 melanoma samples reveals an association of NRAS mutants with bivalent histone H3 lysine 27 trimethylation (H3K27me3) and Polycomb repressive complex 2. Reprogramming of bivalent domains during metastasis occurs on master transcription factors of a mesenchymal phenotype, including ZEB1, TWIST1, and CDH1. Resolution of bivalency using pharmacological inhibition of EZH2 decreases invasive capacity of melanoma cells and markedly reduces tumor burden in vivo, specifically in NRAS mutants. Coincident with bivalent reprogramming, the increased expression of pro-metastatic and melanocyte-specific cell-identity genes is associated with exceptionally wide H3K4me3 domains, suggesting a role for this epigenetic element. Overall, we demonstrate that reprogramming of bivalent and broad domains represents key epigenetic alterations in metastatic melanoma and that EZH2 plus MEK inhibition may provide a promising therapeutic strategy for NRAS mutant melanoma patients.

Indexed as

AnimalsCell Line, TumorCell ProliferationChromatinEnhancer of Zeste Homolog 2 ProteinFemaleGTP PhosphohydrolasesHistonesHumansMelanocytesMelanomaMembrane ProteinsMesodermMiceMice, NudeMitogen-Activated Protein Kinase KinasesChromatinEnhancer of Zeste Homolog 2 ProteinEzh2 protein, mouseGTP Phosphohydrolaseshistone H3 trimethyl Lys4HistonesMembrane ProteinsMitogen-Activated Protein Kinase KinasesNRAS protein, humanPolycomb Repressive Complex 2bivalentbroad domainschromatinepigeneticsmelanomamelanoma therapeuticsmetastasisPolycomb repressive complex 2

Identifiers

PMID34289358
PMCPMC8369408
OpenAlexW3184476714

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.