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Retinoblastoma

Epigenetic outcome

Nature Reviews Cancer volume 12, page 80 (2012)Cite this article

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Knockdown of SYK using short hairpin RNAs indicated that SYK is required for retinoblastoma cell survival

Whole-genome sequencing was carried out on four samples of retinoblastoma from the St Jude Children's Hospital–Washington University Pediatric Cancer Genome Project and the paired normal samples. Interestingly, despite the association of RB1 loss with aneuploidy and chromosomal instability, the four genomes sequenced in this paper were relatively stable. On the basis of these findings, the authors switched their attention to epigenetic alterations. By comparing chromatin immunoprecipitation data, DNA methylation assays and gene expression assays from retinoblastoma with control human retinal samples, 104 genes were shown to have differential expression. One of these, spleen tyrosine kinase (SYK), which is involved in regulating the immune response, had alterations in histone modifications associated with active gene transcription. Moreover, 100% of 82 samples of human retinoblastoma showed increased expression of SYK, as determined by immunohistochemistry. Knockdown of SYK using short hairpin RNAs indicated that SYK is required for retinoblastoma cell survival. Similar results were seen when small-molecule inhibitors of SYK were used in vitro, and addition of a SYK inhibitor prolonged the survival of mice with retinoblastoma orthotopic xenografts treated with topotecan hydrochloride.

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ORIGINAL RESEARCH PAPER

  1. Zhang, J. et al. A novel retinoblastoma therapy from genetic and epigenetic analyses. Nature 11 Jan 2012 (doi:10.1038/nature10733)

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  1. Nicola McCarthy
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McCarthy, N. Epigenetic outcome. Nat Rev Cancer 12, 80 (2012). https://doi.org/10.1038/nrc3222

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