Using DNA probes generated by chromosome microdissection, cDNA microarray analysis, and CGH findings, we have identified a series of chromosomal regions involved in human breast, ovarian and prostate cancer. In order to isolate candidate target genes from these regions, we have developed technologies based on chromosome microdissection, and integrated genome mapping, including DNA microarray analysis. These technologies are being utilized to isolate candidate genes from amplified regions in breast cancer, ovarian cancer, and sarcomas. The methodology previously described illustrates the importance of developing rapid techniques for the identification of genes amplified in a series of key human tumors. In addition to recognizing known sites of gene amplification, we have identified several previously unidentified genes amplified in breast, prostate and ovarian cancers. We are currently focusing on breast cancer where candidate genes can function as coactivators of the estrogen receptor. Their mechanism of action will be studied with model systems based on gene transfer, gene inactivation, and biochemical techniques. In addition, we are developing a comprehensive database of amplified chromosomal regions in soft tissue and bone sarcomas using microarray based CGH. This is a powerful approach for the identification of genes playing a causal role in disease genesis or progression and may provide novel prognostic markers as well as therapeutic targets.
| Wang, Qi; Anzick, Sarah; Richter, William F et al. (2004) Modulation of transcriptional sensitivity of mineralocorticoid and estrogen receptors. J Steroid Biochem Mol Biol 91:197-210 |
| Goo, Young-Hwa; Sohn, Young Chang; Kim, Dae-Hwan et al. (2003) Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins. Mol Cell Biol 23:140-9 |
| Helman, Lee J; Meltzer, Paul (2003) Mechanisms of sarcoma development. Nat Rev Cancer 3:685-94 |
| Borden, Ernest C; Baker, Laurence H; Bell, Robert S et al. (2003) Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res 9:1941-56 |
| Anzick, Sarah L; Azorsa, David O; Simons Jr, S Stoney et al. (2003) Phenotypic alterations in breast cancer cells overexpressing the nuclear receptor co-activator AIB1. BMC Cancer 3:22 |
| Hedenfalk, Ingrid; Ringner, Markus; Ben-Dor, Amir et al. (2003) Molecular classification of familial non-BRCA1/BRCA2 breast cancer. Proc Natl Acad Sci U S A 100:2532-7 |
| Pollock, Pamela M; Cohen-Solal, Karine; Sood, Raman et al. (2003) Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet 34:108-12 |
| Gorlick, Richard; Anderson, Peter; Andrulis, Irene et al. (2003) Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. Clin Cancer Res 9:5442-53 |
| Forozan, F; Veldman, R; Ammerman, C A et al. (1999) Molecular cytogenetic analysis of 11 new breast cancer cell lines. Br J Cancer 81:1328-34 |
