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

نویسندگان

  • 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
  • Robert L. Vessella
  • Tom Walsh
  • Jay Shendure
  • Peter S. Nelson
چکیده

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.

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عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2014