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Status: Bibliographieeintrag

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Verfasst von:Tegeder, Isabel [VerfasserIn]   i
 Erkek, Serap [VerfasserIn]   i
 Johann, Pascal-David [VerfasserIn]   i
 Thatikonda, Venu [VerfasserIn]   i
 Kool, Marcel [VerfasserIn]   i
Titel:Functional relevance of genes predicted to be affected by epigenetic alterations in atypical teratoid/rhabdoid tumors
Verf.angabe:Isabel Tegeder, Katharina Thiel, Serap Erkek, Pascal D. Johann, Johannes Berlandi, Venu Thatikonda, Michael C. Frühwald, Marcel Kool, Astrid Jeibmann, Martin Hasselblatt
Jahr:2019
Jahr des Originals:2018
Umfang:13 S.
Fussnoten:First Online: 16 November 2018 ; Gesehen am 09.05.2019
Titel Quelle:Enthalten in: Journal of neuro-oncology
Ort Quelle:Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983
Jahr Quelle:2019
Band/Heft Quelle:141(2019), 1, Seite 43-55
ISSN Quelle:1573-7373
Abstract:PurposeAtypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly arising in infants. Mutations of SWI/SNF chromatin remodeling complex members SMARCB1/INI1 or (rarely) SMARCA4/Brg1 are the sole recurrent genetic lesions. Epigenetic studies revealed a large number of genes predicted to be affected by differential histone modifications in ATRT, but the role of these genes in the biology of ATRT remains uncertain. We therefore aimed at exploring the role of these genes in the detrimental effects of SMARCB1-deficiency.MethodsThe functional relevance of 1083 genes predicted to be affected by epigenetic alterations in ATRT was examined in vivo using a Drosophila melanogaster model of SMARCB1-deficiency. Human orthologues of genes whose knockdown modified the phenotype in the Gal4-UAS fly model were further examined in ATRT samples and SMARCB1-deficient rhabdoid tumor cells.ResultsKnockdown of Snr1, the fly orthologue of SMARCB1, resulted in a lethal phenotype and epigenetic alterations in the fly model. The lethal phenotype was shifted to later stages of development upon additional siRNA knockdown of 89 of 1083 genes screened in vivo. These included TGF-beta receptor signaling pathway related genes, e.g. CG10348, the fly orthologue of transcriptional regulator PRDM16. Subsequently, PRDM16 was found to be over-expressed in ATRT samples and knockdown of PRDM16 in SMARCB1-deficient rhabdoid tumor cells reduced proliferation.ConclusionsThese results suggest that a subset of genes affected by differential histone modification in ATRT is involved in the detrimental effects of SMARCB1-deficiency and also relevant in the biology of ATRT.
DOI:doi:10.1007/s11060-018-03018-6
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1007/s11060-018-03018-6
 DOI: https://doi.org/10.1007/s11060-018-03018-6
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Drosophila melanogaster
 Histone modifications
 Malignant rhabdoid tumor
 PRDM16
 SMARCB1
 TGFbeta signaling
K10plus-PPN:1665057467
Verknüpfungen:→ Zeitschrift

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