Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nature. 2012 Jan 11;481(7381):329-34. doi: 10.1038/nature10733.

A novel retinoblastoma therapy from genomic and epigenetic analyses.

Author information

  • 1Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

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.

Comment in

PMID:
22237022
[PubMed - indexed for MEDLINE]
PMCID:
PMC3289956
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk