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Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.

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

Author information

1
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA.
2
Department of Urology, University of Washington, Seattle, Washington 98195, USA.
3
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
4
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
5
1] Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
6
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
7
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.

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.

PMID:
25255306
PMCID:
PMC4176888
DOI:
10.1038/ncomms5988
[Indexed for MEDLINE]
Free PMC Article

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