Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster

Astrid Jeibmann, Kristin Eikmeier, Anna Linge, Marcel Kool, Björn Koos, Jacqueline Schulz, Stefanie Albrecht, Kerstin Bartelheim, Michael C. Frühwald, Stefan M. Pfister, Werner Paulus, Martin Hasselblatt

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Article number4005
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 3 Jun 2014
Externally publishedYes

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