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ARF suppression by ...
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Mainwaring, OliverUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Fredrik Swartling
(author)
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2023-03-03
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Springer Nature,2023
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-469075
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-469075URI
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https://doi.org/10.1038/s41467-023-36847-9DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:153826414URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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De två första författarna delar förstaförfattarskapet.
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Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Weishaupt, HolgerUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)holwe849
(author)
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Zhao, MiaoUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)miazh358
(author)
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Rosén, GabrielaUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)gabca335
(author)
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Borgenvik, Anna,1987-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)annbo680
(author)
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Breinschmid, LauraUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
(author)
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Verbaan, Annemieke D.Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
(author)
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Richardson, StaceyWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, NE1 7RU, UK.
(author)
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Thompson, DeanWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, NE1 7RU, UK.
(author)
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Clifford, Steven C.Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, NE1 7RU, UK.
(author)
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Hill, Rebecca M.Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, NE1 7RU, UK.
(author)
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Annusver, KarlKarolinska Institutet
(author)
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Sundström, AndersUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)andsu781
(author)
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Holmberg Olausson, KarlUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)karho832
(author)
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Kasper, MariaKarolinska Institutet
(author)
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Hutter, SonjaUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)sonhu330
(author)
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Swartling, Fredrik J.,1975-Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)fredjoha
(author)
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Uppsala universitetNeuroonkologi
(creator_code:org_t)
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In:Nature Communications: Springer Nature142041-1723
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