Human tumors accumulate a remarkably diverse spectrum of recurrent genomic abnormalities thought to reflect functional reprogramming of the cancer cell phenotype. However, the causes and consequences of many of these abnormalities are unknown. We describe here several mouse-model-based approaches to functional interpretation of these aberrations. Specifically, we demonstrate that integration of information on recurrent aberrations in human breast tumors with information on regions of susceptibility in mice and/or recurrent genomic abnormality in breast tumors that arise in transgenic mice indicates regions of particular importance in human tumors. We also present evidence from analyses of genomic abnormalities in tumors that arise in 'RIP-Tag' transgenic mice that both the genetic background and the temporal dynamics of the initiating oncogenic event significantly affect the spectrum of abnormalities that arises during tumorigenesis.