H3.3 G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumor of Bone.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
24
04
2020
revised:
10
08
2020
accepted:
17
09
2020
pubmed:
25
9
2020
medline:
25
11
2021
entrez:
24
9
2020
Statut:
ppublish
Résumé
Glycine 34-to-tryptophan (G34W) substitutions in H3.3 arise in approximately 90% of giant cell tumor of bone (GCT). Here, we show H3.3 G34W is necessary for tumor formation. By profiling the epigenome, transcriptome, and secreted proteome of patient samples and tumor-derived cells CRISPR-Cas9-edited for H3.3 G34W, we show that H3.3K36me3 loss on mutant H3.3 alters the deposition of the repressive H3K27me3 mark from intergenic to genic regions, beyond areas of H3.3 deposition. This promotes redistribution of other chromatin marks and aberrant transcription, altering cell fate in mesenchymal progenitors and hindering differentiation. Single-cell transcriptomics reveals that H3.3 G34W stromal cells recapitulate a neoplastic trajectory from a
Identifiants
pubmed: 32967858
pii: 2159-8290.CD-20-0461
doi: 10.1158/2159-8290.CD-20-0461
pmc: PMC7710565
mid: NIHMS1632039
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1968-1987Subventions
Organisme : NCI NIH HHS
ID : P01 CA196539
Pays : United States
Organisme : NCRR NIH HHS
ID : P41 RR000862
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA148699
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA159859
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2020 American Association for Cancer Research.
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