Kataegis Expression Signature in Breast Cancer Is Associated with Late Onset, Better Prognosis, and Higher HER2 Levels

Matteo D'Antonio, Pablo Tamayo, Jill P. Mesirov, Kelly A. Frazer

Research output: Contribution to journalArticle

Abstract

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. D'Antonio et al. show kataegis is associated with breast cancer patients diagnosed at an older age and with a higher age at death and in HER2+ tumors. Tumors harboring kataegis are associated with transcriptome-wide expression changes consistent with low invasive potential. Kataegis is a marker for good prognosis in breast cancer.

Original languageEnglish
JournalCell Reports
DOIs
Publication statusAccepted/In press - Jul 29 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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