Journal Article

DKFZ-2017-02180

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster.

Jeibmann, A. ; Eikmeier, K. ; Linge, A. ; Kool, M.DKFZ* ; Koos, B. ; Schulz, J. ; Albrecht, S. ; Bartelheim, K. ; Frühwald, M. C. ; Pfister, S.DKFZ* ; Paulus, W. ; Hasselblatt, M.

2014
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/ncomms5005

Abstract: Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

Keyword(s): Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; Drosophila Proteins ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Neurofibromin 2 ; SMARCB1 Protein ; SMARCB1 protein, human ; Snr1 protein, Drosophila ; Transcription Factors ; Tumor Suppressor Proteins ; expanded protein, Drosophila ; kibra protein, Drosophila ; merlin, Drosophila ; Protein-Serine-Threonine Kinases ; hpo protein, Drosophila

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2014

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