Complex MSH2 and MSH6 Mutations in Hypermutated Microsatellite Unstable Advanced Prostate Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Sep 26

PMID 25255306

Citations 138

Authors

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

Affiliations

Soon will be listed here.

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.

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