Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer
Menée sur 60 échantillons tumoraux prélevés sur des patients atteints d'un cancer de la prostate de stade avancé, cette étude met en évidence des mécanismes associés à une hypermutation du génome, notamment des gènes de réparation des mésappariements de l'ADN
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.