Kataegis Expression Signature in Breast Cancer Is Associated with Late Onset, Better Prognosis, and Higher HER2 Levels
A partir de données portant sur le génome entier de 97 échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein, puis validée sur des données de transcriptome issues de 412 échantillons tumoraux complémentaires, cette étude identifie une signature, basée sur l'expression de gènes localisés dans des régions chromosomiques hypermutées (phénomène de kataegis), en association avec un pronostic favorable
Kataegis is a mutational process observed in ∼55% of breast tumors that results in hypermutation in localized genomic regions. Using whole-genome sequence data of 97 tumors, we examined the distribution of kataegis loci, showing that these somatic mutations are over-represented on chromosomes 8, 17, and 22 and enriched in genic regions and active chromatin elements. We show that tumors harboring kataegis are associated with transcriptome-wide expression changes consistent with low invasive potential. We exploit the kataegis expression signature to predict kataegis status in 412 breast cancers with transcriptome but not whole-genome sequence data and show that kataegis loci are enriched in high-grade, HER2+ tumors in patients diagnosed with breast cancer at an older age and who have a later age at death. Our study demonstrates that kataegis loci are associated with important clinical features in breast cancer and may serve as a marker of good prognosis.
Cell Reports , article en libre accès, 2015