The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome |
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| Authors: | Jens K. Habermann Jana Doering Sampsa Hautaniemi Uwe J. Roblick Nana K. Bündgen Daniel Nicorici Ulrike Kronenwett Shruti Rathnagiriswaran Rama K. R. Mettu Yan Ma Stefan Krüger Hans‐Peter Bruch Gert Auer Nancy L. Guo Thomas Ried |
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| Affiliation: | 1. Genetics Branch, National Cancer Institute, NIH, Bethesda, MD;2. Department of Surgery, University Hospital Schleswig‐Holstein, Campus Lübeck, Lübeck, Germany;3. Karolinska Biomic Center (KBC), Karolinska Institute, Stockholm, Sweden;4. Computational Systems Biology Laboratory, Genome‐Scale Biology Research Program, Biomedicum Helsinki and Institute of Biomedicine, University of Helsinki, Helsinki, Finland;5. Institute of Signal Processing, Tampere University of Technology, Tampere, Finland;6. Department of Community Medicine, MBR Cancer Center, West Virginia University, Morgantown, WV;7. Institute of Pathology, University Hospital Schleswig‐Holstein, Campus Lübeck, Lübeck, Germany;8. Fax: +1‐304‐293‐4667;9. Email:riedt@ mail.nih.gov;12. Fax: +1‐301‐435‐4428 |
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| 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. © 2008 Wiley‐Liss, Inc. |
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| Keywords: | breast cancer gene expression genomic instability aneuploidy prognosis |
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