Category
Research Tools
Diagnostics
Summary of Invention
This invention provides a set of genes that mark, mediate and predict the propensity of breast cancer to metastasize selectively to the lung, a frequent site of breast cancer metastasis. This set of genes, or a subset, can be used to develop transcriptomic-based prognostic tests to help tailor a treatment course in breast cancer patients. It can also be used to develop targeted therapies (siRNA, drugs, antibodies, etc) against one or more of these genes or their corresponding proteins. The set consists of 54 genes, although a subset of 18 genes has a very similar prognostic value. Some of these genes serve lung metastagenicity functions whereas others confer metastatic virulence. Many encode extracellular proteins and most are of previously unknown relevance to cancer metastasis.
To obtain the gene set of this invention, MDA-MB-231 cells were tailvein-injected into immunodeficient mice. Lung lesions were twice expanded in culture and re-inoculated into mice, after which highly metastatic cells were obtained. These cells were compared to the parental cell line by transcriptomic microarray. Genes that had 3-fold or higher change in expression level were selected, after eliminating genes that were expressed at low levels, and a final set of 54 genes was obtained. Clustering of a data set of primary breast tumors identified subgroups that express a similar signature than the highly metastatic cell line, validating the model.
A selected group of the overexpressed genes of the set was transfected into the parental population, either individually or in groups. Combinations of these genes invariably led to more aggressive metastatic activity, some even recapitulated the aggressiveness of the highly metastatic cell line. Moreover, the necessity of some of these genes for metastasis was demonstrated by stably decreasing their expression using siRNAs and finding in many cases a concomitant reduction of 10 fold or more in metastatic potential. Collectively, the results show that these genes are not only markers but also mediators of lung-specific metastasis
Advantage
- Transcriptomic-based prognostic tests to help tailor treatment course in breast cancer patients
- In vitro validated breast cancer metastasis target genes to use as research tool for new therapies
Areas of Application
Breast cancer prognosis, research tool.
Lead Inventor
Joan Massague
Patent Information
- US patent application published
- PCT patent application published WO 2006/074367
References
Minn AJ, et al. (2005) Nature Jul 28;436:518-24
Contact Information
Lisa Placanica, PhD
Tel: 212-639-6181; Fax: 212-717-3739
E-mail: placanil@mskcc.org
