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    The expression level of small non-coding RNAs derived from the first exon of protein-coding genes is predictive of cancer status

    Access Status
    Open access via publisher
    Authors
    Zovoilis, A.
    Mungall, A.
    Moore, R.
    Varhol, Richard
    Chu, A.
    Wong, T.
    Marra, M.
    Jones, S.
    Date
    2014
    Type
    Journal Article
    
    Metadata
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    Citation
    Zovoilis, A. and Mungall, A. and Moore, R. and Varhol, R. and Chu, A. and Wong, T. and Marra, M. et al. 2014. The expression level of small non-coding RNAs derived from the first exon of protein-coding genes is predictive of cancer status. EMBO Reports. 15 (4): pp. 402-410.
    Source Title
    EMBO Reports
    DOI
    10.1002/embr.201337950
    ISSN
    1469-221X
    School
    Department of Health Policy and Management
    URI
    http://hdl.handle.net/20.500.11937/37817
    Collection
    • Curtin Research Publications
    Abstract

    Small non-coding RNAs (smRNAs) are known to be significantly enriched near the transcriptional start sites of genes. However, the functional relevance of these smRNAs remains unclear, and they have not been associated with human disease. Within the cancer genome atlas project (TCGA), we have generated small RNA datasets for many tumor types. In prior cancer studies, these RNAs have been regarded as transcriptional "noise," due to their apparent chaotic distribution. In contrast, we demonstrate their striking potential to distinguish efficiently between cancer and normal tissues and classify patients with cancer to subgroups of distinct survival outcomes. This potential to predict cancer status is restricted to a subset of these smRNAs, which is encoded within the first exon of genes, highly enriched within CpG islands and negatively correlated with DNA methylation levels. Thus, our data show that genome-wide changes in the expression levels of small non-coding RNAs within first exons are associated with cancer. Synopsis The expression of small non-coding RNAs encoded within the first exon of genes can be used to efficiently identify cancer samples and classify patients into subgroups of different survival. Such pan-cancer association is the first link between these RNAs and disease. Exon 1 small non-coding RNAs (smRNAs) can distinguish between cancer and normal tissues. The prediction potential of exon 1 smRNAs differs from that of other smRNAs around transcriptional start sites (TSS). smRNA locations around TSS are conserved between different individuals. smRNA locations are enriched within CpG islands and their levels negatively correlated with DNA methylation. The expression of small non-coding RNAs encoded within the first exon of genes can be used to efficiently identify cancer samples and classify patients into subgroups of different survival. Such pan-cancer association is the first link between these RNAs and disease. © 2014 The Authors.

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