Keynote Address: Blueprint of the Breast and Colorectal Cancer Genomes

KN-01

It is widely accepted that human cancer is a genetic disease caused by accumulation of mutations in oncogenes and tumor suppressor genes. These tumor-specific mutations provide clues to the cellular processes underlying tumorigenesis and have proven useful for diagnostic and therapeutic purposes. To date, however, only a small fraction of the genes has been analyzed and the number and type of alterations responsible for the development of common tumor types are unknown. The determination of the human genome sequence coupled with improvements in sequencing and bioinformatic approaches have now made it possible, in principle, to examine the cancer cell genome in a comprehensive and unbiased manner. We have begun a systematic study of the cancer genome through examination of gene families involved in signal transduction. These efforts have identified frequent activating mutations in a number of different kinases and phosphatases not previously linked to human cancer. For example, we have found genetic alterations in the PIK3CA gene encoding the p110 alpha phosphatidylinositol 3-kinase in ~30% of colon and breast cancers, providing a rational target for therapy in a large fraction of common malignancies. These studies have recently been extended to genome-wide analyses of the protein coding genes in breast and colorectal cancer. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.