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https://hdl.handle.net/2440/126759
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Type: | Journal article |
Title: | A novel retinoblastoma therapy from genomic and epigenetic analyses |
Author: | Zhang, J. Benavente, C.A. McEvoy, J. Flores-Otero, J. Ding, L. Chen, X. Ulyanov, A. Wu, G. Wilson, M. Wang, J. Brennan, R. Rusch, M. Manning, A.L. Ma, J. Easton, J. Shurtleff, S. Mullighan, C. Pounds, S. Mukatira, S. Gupta, P. et al. |
Citation: | Nature, 2012; 481(7381):329-334 |
Publisher: | Nature Publishing Group |
Issue Date: | 2012 |
ISSN: | 0028-0836 1476-4687 |
Statement of Responsibility: | Jinghui Zhang, Claudia A. Benavente, Justina McEvoy, Jacqueline Flores-Otero, Li Ding ... Charles Mullighan ... et al. |
Abstract: | Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss. |
Keywords: | Cell Line |
Rights: | ©2012 Macmillan Publishers Limited. All rights reserved |
DOI: | 10.1038/nature10733 |
Published version: | http://dx.doi.org/10.1038/nature10733 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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