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Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer

Author

Listed:
  • Colin C. Pritchard

    (University of Washington)

  • Colm Morrissey

    (University of Washington)

  • Akash Kumar

    (University of Washington)

  • Xiaotun Zhang

    (University of Washington)

  • Christina Smith

    (University of Washington)

  • Ilsa Coleman

    (Fred Hutchinson Cancer Research Center)

  • Stephen J. Salipante

    (University of Washington
    University of Washington)

  • Jennifer Milbank

    (University of Washington)

  • Ming Yu

    (Fred Hutchinson Cancer Research Center)

  • William M. Grady

    (Fred Hutchinson Cancer Research Center)

  • Jonathan F. Tait

    (University of Washington)

  • Eva Corey

    (University of Washington)

  • Robert L. Vessella

    (University of Washington)

  • Tom Walsh

    (University of Washington)

  • Jay Shendure

    (University of Washington)

  • Peter S. Nelson

    (Fred Hutchinson Cancer Research Center)

Abstract

A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers.

Suggested Citation

  • Colin C. Pritchard & Colm Morrissey & Akash Kumar & Xiaotun Zhang & Christina Smith & Ilsa Coleman & Stephen J. Salipante & Jennifer Milbank & Ming Yu & William M. Grady & Jonathan F. Tait & Eva Corey, 2014. "Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer," Nature Communications, Nature, vol. 5(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5988
    DOI: 10.1038/ncomms5988
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    Cited by:

    1. Yuqian Liu & Yan Chen & Huanwen Wu & Xuanping Zhang & Yuqi Wang & Xin Yi & Zhiyong Liang & Jiayin Wang, 2024. "scMSI: Accurately inferring the sub-clonal Micro-Satellite status by an integrated deconvolution model on length spectrum," PLOS Computational Biology, Public Library of Science, vol. 20(12), pages 1-21, December.

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