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Cell Rep. 2016 Jul 19;16(3):672-83. doi: 10.1016/j.celrep.2016.06.026. Epub 2016 Jun 30.

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

Author information

1
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
2
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
4
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics and Rady Children's Hospital, Division of Genome Information Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: kafrazer@ucsd.edu.

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.

PMID:
27373164
PMCID:
PMC4972030
DOI:
10.1016/j.celrep.2016.06.026
[Indexed for MEDLINE]
Free PMC Article

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