title: Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster.
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.
authors.affiliation: 1] Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany [2].
authors.forename: Astrid
authors.initials: A
authors.lastname: Jeibmann
authors.affiliation: 1] Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany [2].
authors.forename: Kristin
authors.initials: K
authors.lastname: Eikmeier
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Linge
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Box 815, 75108 Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Koos
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schulz
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Albrecht
authors.affiliation: Swabian Childrens' Cancer Center, Childrens' Hospital Augsburg and EU-RHAB Registry, Stenglinstr. 2, 86156 Augsburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bartelheim
authors.affiliation: Swabian Childrens' Cancer Center, Childrens' Hospital Augsburg and EU-RHAB Registry, Stenglinstr. 2, 86156 Augsburg, Germany.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D025581:Neurofibromin 2 / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D015398:Signal Transduction; D013724:Teratoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000099317:Hippo Kinases
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D025581:Neurofibromin 2; D017346:Protein Serine-Threonine Kinases; D000071796:SMARCB1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C513266:SMARCB1 protein, human; C096659:Snr1 protein, Drosophila; C085090:ex protein, Drosophila; C548168:kibra protein, Drosophila; C099885:merlin, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases