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

被引：30

作者：

D'Antonio, Matteo ^{[1
]}

Tamayo, Pablo ^{[1
,2
]}

Mesirov, Jill P. ^{[2
]}

Frazer, Kelly A. ^{[1
,3
,4
,5
]}

机构：

[1] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Rady Childrens Hosp, Div Genome Informat Sci, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

来源：

CELL REPORTS | 2016年 / 16卷 / 03期

关键词：

MUTATIONAL PROCESSES; RISK; REGRESSION; DISCOVERY; SUBTYPES; REVEALS; GENOMES; CELLS;

D O I：

10.1016/j.celrep.2016.06.026

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Kataegis is a mutational process observed in similar to 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 highgrade, 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.

引用

页码：672 / 683

页数：12

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