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Multiple Interacting Oncogenes on the 8p11-p12 Amplicon in Human Breast Cancer

¹ Breast Cancer Program; ² Biostatistics Core, Department of Pathology, Karmanos Cancer Institute; ³ Wayne State University School of Medicine, Detroit, Michigan; and ⁴ Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan

Requests for reprints: Stephen P. Ethier, Barbara Ann Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201. Phone: 313-576-8613; Fax: 313-576-8626; E-mail: ethier{at}karmanos.org.

The 8p11-p12 genomic region is amplified in 15% of breast cancers and harbors several candidate oncogenes. However, functional evidence for a transforming role for these genes is lacking. We identified 21 genes from this region as potential oncogenes based on statistical association between copy number and expression. We further showed that three of these genes (LSM1, BAG4, and C8orf4) induce transformed phenotypes when overexpressed in MCF-10A cells, and overexpression of these genes in combination influences the growth factor independence phenotype and the ability of the cells to grow under anchorage-independent conditions. Thus, LSM1, BAG4, and C8orf4 are breast cancer oncogenes that can work in combination to influence the transformed phenotype in human mammary epithelial cells. (Cancer Res 2006; 66(24): 11632-42)

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