Evidence map›Paper›PMID 33110075›Full record

ArticleNature communications2020

Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone.

Pavlo Lutsik, Annika Baude, Daniela Mancarella, Simin Öz, Alexander Kühn, Reka Toth, Joschka Hey, Umut H Toprak, Jinyeong Lim, Viet Ha Nguyen and 23 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
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

31 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
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  3. Article
  4. Observational
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  9. Review
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  11. Article
  12. [Giant cell tumor of bone-an update].Pathologie (Heidelberg, Germany) · 2023
    Review
  13. Histone mutations in cancer.Biochemical Society transactions · 2023
    Article
  14. Review
  15. Article
  16. 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

33 authors at 10 institutions in 4 countries.

Pavlo LutsikDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.ORCID 0000-0001-9383-8555
Annika BaudeDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Daniela MancarellaDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Simin ÖzDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Alexander KühnDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Reka TothDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Joschka HeyDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.ORCID 0000-0003-2842-764X
Umut H ToprakBioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Jinyeong LimGraduate School of Cancer Science and Policy, Cancer Biomedical Science, National Cancer Center, Goyang-si, Gyeonggi-do, 10408, Republic of Korea, Republic of Korea.ORCID 0000-0001-9358-9552
Viet Ha NguyenGraduate School of Cancer Science and Policy, Cancer Biomedical Science, National Cancer Center, Goyang-si, Gyeonggi-do, 10408, Republic of Korea, Republic of Korea.
Chao JiangBotnar Research Centre, Oxford NIHR BRC, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.
Anand MayakondaDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Mark HartmannSection Translational Cancer Epigenomics, Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) & German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.ORCID 0000-0002-4072-4658
Felix RosemannDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.ORCID 0000-0002-1649-3247
Kersten BreuerDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.ORCID 0000-0003-3716-7739
Dominik VonfichtFaculty of Biosciences, Ruprecht Karl University of Heidelberg, Im Neuenheimer Feld 234, 69120, Heidelberg, Germany.
Florian GrünschlägerFaculty of Biosciences, Ruprecht Karl University of Heidelberg, Im Neuenheimer Feld 234, 69120, Heidelberg, Germany.
Suman LeeGraduate School of Cancer Science and Policy, Cancer Biomedical Science, National Cancer Center, Goyang-si, Gyeonggi-do, 10408, Republic of Korea, Republic of Korea.
Maren Kirstin SchuhmacherDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Denis KusevicDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Anna JauchInstitute of Human Genetics, Ruprecht Karl University of Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany.
Dieter WeichenhanDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Jozef ZustinInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20251, Hamburg, Germany.
Matthias SchlesnerBioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.ORCID 0000-0002-5896-4086
Simon HaasDivision of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Joo Hyun ParkDepartment of Nutritional Science and Food Management, Ewha Womans University, 52 Ewhayeodae-gil, Daehyeon-dong, Seodaemun-gu, Seoul, 03760, Republic of Korea.
Yoon Jung ParkDepartment of Nutritional Science and Food Management, Ewha Womans University, 52 Ewhayeodae-gil, Daehyeon-dong, Seodaemun-gu, Seoul, 03760, Republic of Korea.
Udo OppermannBotnar Research Centre, Oxford NIHR BRC, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.ORCID 0000-0001-9984-5342
Albert JeltschDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID 0000-0001-6113-9290
Florian HallerInstitute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg, Krankenstrasse 8, 91054, Erlangen, Germany.ORCID 0000-0002-0148-3273
Jörg FellenbergDepartment of Experimental Orthopaedics, Orthopaedic University Hospital Heidelberg, Ruprecht Karl University of Heidelberg, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany.
Anders M LindrothGraduate School of Cancer Science and Policy, Cancer Biomedical Science, National Cancer Center, Goyang-si, Gyeonggi-do, 10408, Republic of Korea, Republic of Korea. lindroth@ncc.re.kr.ORCID 0000-0002-8291-2745
Christoph PlassDivision of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. c.plass@dkfz.de.ORCID 0000-0003-2554-3952
German Cancer Research Center · DENational Cancer Center · KRUniversity of Stuttgart · DEEwha Womans University · KRHeidelberg University · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DENational Cancer Center · USNuffield Orthopaedic Centre · GBUniversität Hamburg · DEUniversity of Freiburg · DE

Funding

Arthritis Research UK 20522Department of HealthVersus Arthritis 20522
6 · The paper itself

Abstract

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level, that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability, as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W-associated changes.

Indexed as

OsteogenesisBone NeoplasmsDNA MethylationEpigenesis, GeneticEpigenomicsGiant Cell Tumor of BoneHistonesHumansMutation, MissenseHistones

Identifiers

PMID33110075
PMCPMC7591516
OpenAlexW3095227626

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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.