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Molecular Biology and Genetics |
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 [K. J. M., B. M. K., L. M. P., B. K., C-P. K., X. Z., A. B. P., R. S.]; Ludwig Institute for Cancer Research/University College London, Breast Cancer Laboratory, University College London Medical School, London W1P 6DB, United Kingdom [A. M., M. J. O.]; and Departments of Surgery [C. M. K.] and Pathology [G. L. M.], Brigham and Women’s Hospital, Boston, Massachusetts 02115
A major objective of current cancer research is to develop a detailed molecular characterization of tumor cells and tissues that is linked to clinical information. Toward this end, we have identified approximately one-quarter of all genes that were aberrantly expressed in a breast cancer cell line using differential display. The cancer cells lost the expression of many genes involved in cell adhesion, communication, and maintenance of cell shape, while they gained the expression of many synthetic and metabolic enzymes important for cell proliferation. High-density, membrane-based hybridization arrays were used to study mRNA expression patterns of these genes in cultured cells and archived tumor tissue. Cluster analysis was then used to identify groups of genes, the expression patterns of which correlated with clinical information. Two clusters of genes, represented by p53 and maspin, had expression patterns that strongly associated with estrogen receptor status. A third cluster that included HSP-90 tended to be associated with clinical tumor stage, whereas a forth cluster that included keratin 14 tended to be associated with tumor size. Expression levels of these clinically relevant gene clusters allowed breast tumors to be grouped into distinct categories. Gene expression fingerprints that include these four gene clusters have the potential to improve prognostic accuracy and therapeutic outcomes for breast cancer patients.
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