From chromosomal alterations to target genes for therapy: integrating cytogenetic and functional genomic views of the breast cancer genome

A vast number of recurrent chromosomal alterations have been implicated in cancer development and progression. However, most of the genes involved in recurrent chromosomal alterations in solid tumors remain unknown, despite t he recent substantial progress in genomic research and availability of high -throughput technologies. For example, it is now possible to quickly identi fy large numbers of differentially expressed genes in cancer specimens usin g cDNA microarrays. Integration of this 'functional genomic view' of the ca ncer genome with the 'cytogenetic view' could lead to the identification of genes Playing a critical role in cancer development and progression. In th is review, we illustrate how the combination of three different microarray technologies, cDNA, CGH, and tissue microarrays, makes it possible to direc tly identify genes involved in chromosomal rearrangements in cell line mode l systems and then rapidly explore their significance as potential diagnost ic and therapeutic targets in human Primary breast cancer Progression.