TY - JOUR
T1 - Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster
AU - Jeibmann, Astrid
AU - Eikmeier, Kristin
AU - Linge, Anna
AU - Kool, Marcel
AU - Koos, Björn
AU - Schulz, Jacqueline
AU - Albrecht, Stefanie
AU - Bartelheim, Kerstin
AU - Frühwald, Michael C.
AU - Pfister, Stefan M.
AU - Paulus, Werner
AU - Hasselblatt, Martin
N1 - Funding Information:
This work was supported by IZKF Münster (Ha3/016/11), DFG (Pa 328/7) and Deutsche Krebshilfe (110266). B.K. is supported by Deutsche Forschungsgemeinschaft (Ko 4345/1-1). The EU-RHAB registry is supported by Deutsche Kinderkrebsstiftung.
PY - 2014/6/3
Y1 - 2014/6/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84901937026&partnerID=8YFLogxK
U2 - 10.1038/ncomms5005
DO - 10.1038/ncomms5005
M3 - Article
C2 - 24892285
AN - SCOPUS:84901937026
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 4005
ER -