title: The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome.
abstract: Recently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the 2 groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets, such as luminal A and B, basal, normal-like, and ERBB2+, and prognostic signatures including MammaPrint and Oncotype DX, predicted genomic instability in our samples. This remarkable congruence suggests a biological interdependence of poor-prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome.
authors.affiliation: Genetics Branch, National Cancer Institute, NIH, Bethesda, MD 20892-8010, USA.
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
authors.forename: Jana
authors.initials: J
authors.lastname: Doering
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Nana K
authors.initials: NK
authors.lastname: Bündgen
authors.forename: Daniel
authors.initials: D
authors.lastname: Nicorici
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kronenwett
authors.forename: Shruti
authors.initials: S
authors.lastname: Rathnagiriswaran
authors.forename: Rama K R
authors.initials: RK
authors.lastname: Mettu
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Guo
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis