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@ARTICLE{Tegeder:141761,
author = {I. Tegeder and K. Thiel and S. Erkek$^*$ and P. Johann$^*$
and J. Berlandi and V. Thatikonda$^*$ and M. C. Frühwald
and M. Kool$^*$ and A. Jeibmann and M. Hasselblatt},
title = {{F}unctional relevance of genes predicted to be affected by
epigenetic alterations in atypical teratoid/rhabdoid
tumors.},
journal = {Journal of neuro-oncology},
volume = {141},
number = {1},
issn = {1573-7373},
address = {Dordrecht [u.a.]},
publisher = {Springer Science + Business Media B.V},
reportid = {DKFZ-2018-02030},
pages = {43-55},
year = {2019},
abstract = {Atypical 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.The 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.Knockdown 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.These 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.},
cin = {B062 / L101},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30446899},
doi = {10.1007/s11060-018-03018-6},
url = {https://inrepo02.dkfz.de/record/141761},
}