Carcinogenesis Advance Access published online on May 20, 2008
Carcinogenesis, doi:10.1093/carcin/bgn096
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Defining the blueprint of the cancer genome
Ludwig Center for Cancer Genetics and Therapeutics The Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
Correspondence should be addressed to velculescu{at}jhmi.edu
It is widely accepted that cancer is a disease caused by accumulation of mutations in specific 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 made it possible to examine the cancer cell genome in a comprehensive and unbiased manner. Systematic sequencing studies have been performed on gene families involved in signal transduction in several tumor types, and have now been extended to include the majority of protein coding genes in breast and colorectal cancers. These analyses have identified new genes and pathways that had not been previously linked to human cancer. One example has been the identification of genetic alterations in the PIK3CA gene encoding p110 alpha phosphatidylinositol 3-kinase and in related pathway genes in >30% of colon and breast cancers. These mutational analyses provide a window into the genetic landscape of human cancer, indicate new targets for personalized diagnostic and therapeutic intervention, and suggest lessons for future large-scale genomic analyses in human tumors.
Received April 7, 2008; revised April 7, 2008; accepted April 7, 2008.