title: Kataegis Expression Signature in Breast Cancer Is Associated with Late Onset, Better Prognosis, and Higher HER2 Levels.
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.
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Antonio
authors.affiliation: 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.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tamayo
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.affiliation: 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.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Frazer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics; D000073336:Whole Genome Sequencing / Q000379:methods
chemical_list: D002843:Chromatin; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human