Genome wide studies of breast cancer: A bioinf. and genetic appr. to understand gene reg. and dysreg. in breast tumor development and progr.

The fundamental defects in cancer are alterations in the genome. Microarray-based Comparative Genome Hybridization (array CGH) provides the possibility to connect DNA copy-aberrations with genomic map positions. In a first attempt to compare data from di fferent types of CGH techniques, samples from 8 breast tumors were analyzed using classical CGH, two different set of array CGH (based on 500 and 2.400 BAC clone arrays) and a cDNA array containing 6700 mapped human genes. mRNA expression profiles from th e same tumors were also available. In close collaboration with the Institute of Informatics (University of Oslo), University of California San Francisco (UCSF) and the Stanford University a comparative study of the methods is performed based on state-of-t he-art statistical modeling and analysis methods. Further we want to identify genes that are dysregulated by other mechanisms than copy number alterations, determine their characteristics and explore the underlying mechanism of variation in gene expression. By performing real-time quantitative R T-PCR assay we will investigate the response of specific human breast tumor marker genes and the impact of genes coding for mRNA binding proteins, like CRD-BP (Coding Region instability Determinant Binding Protein) that stabilizes myc mRNA, to the treatm ent with DOXO or FUMI. The growing list of RNA-binding proteins influencing carcinogenesis is striking and we hypothesize that other mRNA binding proteins are present and related to tumorigenesis. This seems to be not only an interesting feature for cance r diagnostic and therapeutic issues but also for the biological understanding of the mechanisms of gene regulating as such.