APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Brian A. Walker, Christopher P. Wardell, Alex Murison, Eileen M. Boyle, Dil B. Begum, Nasrin M. Dahir, Paula Z. Proszek, Lorenzo Melchor, Charlotte Pawlyn, Martin F. Kaiser, David C. Johnson, Ya-Wei Qiang, John R. Jones, David A. Cairns, Walter M. Gregory, Roger G. Owen, Gordon Cook, Mark T. Drayson, Graham H. Jackson, Faith E. Davies, Gareth J. Morgan

ABSTRACT

We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutational signature is seen in 3.8% of cases and is linked to the translocation-mediated deregulation of MAF and MAFB, a known poor prognostic factor. Patients with this signature have an increased mutational load and a poor prognosis. Loss of MAF or MAFB expression results in decreased APOBEC3B and APOBEC4 expression, indicating a transcriptional control mechanism. Kataegis, a further mutational pattern associated with APOBEC deregulation, is seen at the sites of the MYC translocation. The APOBEC mutational signature seen in myeloma is, therefore, associated with poor prognosis primary and secondary translocations and the molecular mechanisms involved in generating them. More... »

PAGES

6997

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms7997

    DOI

    http://dx.doi.org/10.1038/ncomms7997

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1020039215

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25904160


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