Molecular portraits of breast cancer: Translating genomics to the clinical practice.

Project leader and key members:
Therese Sørlie
Aslaug Muggerud
Anna Bergamaschi
Anne-Lise Børresen-Dale

Home address Internet:
http://radium.no/borresen/index.php?aid=2743&k=borresen%2FGroup+members&mid=1

Department:
Department of Genetics, Institute for Cancer Research

Main aim project:
The overall goal of this project is to identify individual gene targets and sets of genes that contribute to the potential of breast cancer to be aggressive and metastatic, and genes that reflect and predict treatment responses. We will apply state-of-the-art microarray tools, novel functional technologies and associated statistical and bioinformatics methods to profile breast tumors at the DNA, RNA and protein level.

Important results:
Gene expression profiles measured by using DNA microarrays have the power of capturing the complexities of tumors and can be used to portray a tumor’s detailed phenotype in its unique context. This may provide a basis for an improved molecular taxonomy of breast cancer. We were the first to identify five subtypes of breast tumors characterized by specific expression patterns by using hierarchical clustering of global gene expression data. This is a fundamentally important discovery, which has also been validated in other studies. These molecular subtypes were associated with significant differences in overall and relapse-free survival for the patients. Furthermore, we found evidence for the presence of these subtypes in two independent data sets comprising different patient populations whose gene expression profiles had been determined using different microarray technology platforms.

1. Perou, C. M., Sorlie, T., Eisen, M. B., van de, R. M., Jeffrey, S. S., Rees, C. A., Pollack, J. R., Ross, D. T., Johnsen, H., Akslen, L. A. et al. (2000) Nature 406, 747-752.
2. Sorlie, T., Perou, C. M., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M. B., van de, R. M., Jeffrey, S. S. et al. (2001) Proc Natl Acad Sci U S A 98, 10869-10874.
3. Sorlie, T., Tibshirani, R., Parker, J., Hastie, T., Marron, J. S., Nobel, A., Deng, S., Johnsen, H., Pesich, R., Geisler, S. et al. (2003) Proc. Natl. Acad. Sci. U. S. A 100, 8418-8423.

Methods:
DNA micrarrays for analyzing both gene expression patterns and genomic changes in cancer
Quantitative RT-PCR
SNP analyses on a genomic scale
siRNA technology

Equipment:
DNA microarray platforms
QRT-PCR technology
Capllary sequencing

Collaborators Helse Sør:
Professor Jahn Nesland, The Norwegian Radium Hospital
Dr Bjørn Naume, The Norwegian Radium Hospital

Collaborators other:
Professor Per E. Lønning, Haukeland University
Professor Arnoldo Frigessi, Univeristy of Oslo

Collaborators other countries:
Professor David Botstein, Princeton University
Professor Patrick O. Brown, Stanford University
Dr Jonathan Pollack, Stanford University
Professor Olli Kallioniemi, VTT Medical Biotechnology, Finland
Professor Robert Tibshirani, Stanford University

Key search words:
Breast cancer
DNA microarrays
Cancer genomics