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

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.

SUBMITTER: Pritchard CC

PROVIDER: S-EPMC4176888 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Pritchard Colin C CC Morrissey Colm C Kumar Akash A Zhang Xiaotun X Smith Christina C Coleman Ilsa I Salipante Stephen J SJ Milbank Jennifer J Yu Ming M Grady William M WM Tait Jonathan F JF Corey Eva E Vessella Robert L RL Walsh Tom T Shendure Jay J Nelson Peter S PS

Nature communications 20140925

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 mechanis ...[more]

PMID: 25255306

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