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

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 ep...

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Autores principales: Lutsik, Pavlo, Baude, Annika, Mancarella, Daniela, Öz, Simin, Kühn, Alexander, Toth, Reka, Hey, Joschka, Toprak, Umut H., Lim, Jinyeong, Nguyen, Viet Ha, Jiang, Chao, Mayakonda, Anand, Hartmann, Mark, Rosemann, Felix, Breuer, Kersten, Vonficht, Dominik, Grünschläger, Florian, Lee, Suman, Schuhmacher, Maren Kirstin, Kusevic, Denis, Jauch, Anna, Weichenhan, Dieter, Zustin, Jozef, Schlesner, Matthias, Haas, Simon, Park, Joo Hyun, Park, Yoon Jung, Oppermann, Udo, Jeltsch, Albert, Haller, Florian, Fellenberg, Jörg, Lindroth, Anders M., Plass, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591516/
https://www.ncbi.nlm.nih.gov/pubmed/33110075
http://dx.doi.org/10.1038/s41467-020-18955-y
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author Lutsik, Pavlo
Baude, Annika
Mancarella, Daniela
Öz, Simin
Kühn, Alexander
Toth, Reka
Hey, Joschka
Toprak, Umut H.
Lim, Jinyeong
Nguyen, Viet Ha
Jiang, Chao
Mayakonda, Anand
Hartmann, Mark
Rosemann, Felix
Breuer, Kersten
Vonficht, Dominik
Grünschläger, Florian
Lee, Suman
Schuhmacher, Maren Kirstin
Kusevic, Denis
Jauch, Anna
Weichenhan, Dieter
Zustin, Jozef
Schlesner, Matthias
Haas, Simon
Park, Joo Hyun
Park, Yoon Jung
Oppermann, Udo
Jeltsch, Albert
Haller, Florian
Fellenberg, Jörg
Lindroth, Anders M.
Plass, Christoph
author_facet Lutsik, Pavlo
Baude, Annika
Mancarella, Daniela
Öz, Simin
Kühn, Alexander
Toth, Reka
Hey, Joschka
Toprak, Umut H.
Lim, Jinyeong
Nguyen, Viet Ha
Jiang, Chao
Mayakonda, Anand
Hartmann, Mark
Rosemann, Felix
Breuer, Kersten
Vonficht, Dominik
Grünschläger, Florian
Lee, Suman
Schuhmacher, Maren Kirstin
Kusevic, Denis
Jauch, Anna
Weichenhan, Dieter
Zustin, Jozef
Schlesner, Matthias
Haas, Simon
Park, Joo Hyun
Park, Yoon Jung
Oppermann, Udo
Jeltsch, Albert
Haller, Florian
Fellenberg, Jörg
Lindroth, Anders M.
Plass, Christoph
author_sort Lutsik, Pavlo
collection PubMed
description 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.
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spelling pubmed-75915162020-11-10 Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone Lutsik, Pavlo Baude, Annika Mancarella, Daniela Öz, Simin Kühn, Alexander Toth, Reka Hey, Joschka Toprak, Umut H. Lim, Jinyeong Nguyen, Viet Ha Jiang, Chao Mayakonda, Anand Hartmann, Mark Rosemann, Felix Breuer, Kersten Vonficht, Dominik Grünschläger, Florian Lee, Suman Schuhmacher, Maren Kirstin Kusevic, Denis Jauch, Anna Weichenhan, Dieter Zustin, Jozef Schlesner, Matthias Haas, Simon Park, Joo Hyun Park, Yoon Jung Oppermann, Udo Jeltsch, Albert Haller, Florian Fellenberg, Jörg Lindroth, Anders M. Plass, Christoph Nat Commun Article 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. Nature Publishing Group UK 2020-10-27 /pmc/articles/PMC7591516/ /pubmed/33110075 http://dx.doi.org/10.1038/s41467-020-18955-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lutsik, Pavlo
Baude, Annika
Mancarella, Daniela
Öz, Simin
Kühn, Alexander
Toth, Reka
Hey, Joschka
Toprak, Umut H.
Lim, Jinyeong
Nguyen, Viet Ha
Jiang, Chao
Mayakonda, Anand
Hartmann, Mark
Rosemann, Felix
Breuer, Kersten
Vonficht, Dominik
Grünschläger, Florian
Lee, Suman
Schuhmacher, Maren Kirstin
Kusevic, Denis
Jauch, Anna
Weichenhan, Dieter
Zustin, Jozef
Schlesner, Matthias
Haas, Simon
Park, Joo Hyun
Park, Yoon Jung
Oppermann, Udo
Jeltsch, Albert
Haller, Florian
Fellenberg, Jörg
Lindroth, Anders M.
Plass, Christoph
Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
title Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
title_full Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
title_fullStr Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
title_full_unstemmed Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
title_short Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
title_sort globally altered epigenetic landscape and delayed osteogenic differentiation in h3.3-g34w-mutant giant cell tumor of bone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591516/
https://www.ncbi.nlm.nih.gov/pubmed/33110075
http://dx.doi.org/10.1038/s41467-020-18955-y
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