Cancer: A Disease of the Genome
Authors: Francis Collins
Journal: Cancer Research (2007)

PL01-01  Decades of research into genetics and molecular biology of cancer are painting an increasingly detailed picture of the molecular basis of the disease, confirming that cancer is clearly a disease of the genome. Some of the genetic factors are hereditary, but most represent somatic mutations acquired during life in tumor suppressor genes, oncogenes, or genes affecting DNA stability. These molecular revelations are increasingly being translated into diagnostic and therapeutic tools.  The full characterization of the cancer cell represents our best hope for the ultimate conquest of this disease. The time is now right for applying the increasingly powerful tools of genomics, arising from the Human Genome Project, to achieve a comprehensive molecular characterization of cancer. Accordingly, the National Cancer Institute and the National Human Genome Research Institute have joined together to initiate a bold new program - The Cancer Genome Atlas (TCGA). Beginning as a three-year pilot project, TCGA is bringing together investigators with a wide range of clinical and basic science skills and asking them to apply these technologies to a full characterization of three cancer types, using a open data access model which will empower many investigators around the world (see http://www.cancergenome.nih.gov). The components of TCGA include 1) a Biospecimen Repository where tumor specimens will be characterized and biomolecules prepared for analysis; 2) a sequencing of tumor DNA (and control DNA from the same individual), to be conducted by three DNA sequencing centers, focused initially on a candidate gene list appropriate for the particular tumor at hand, but ultimately aiming to extend this list to include the entire genome; and 3) a series of seven Cancer Genome Characterization Centers (CGCCs) that will apply a wide variety of high throughput technologies to look at copy number changes, gene expression and epigenetic alterations in the tumors. All of the data will be quality-checked and made rapidly accessible to the scientific community, through the caBIG database supported by the National Cancer Institute.  The initial tumors chosen for study are glioblastoma multiforme, squamous cell lung cancer, and ovarian cancer. Approximately 500 tumors of each type will be studied during the three year pilot period. A “pre-pilot” project supported by NHGRI has been conducting similar analyses on adenocarcinoma of the lung and has already uncovered important findings based upon this kind of comprehensive genomic analysis. This experience adds further confidence that the coordinated, multi-disciplinary, technologically advanced and open data access approach to highly characterized tumors will yield many new findings.  Uncovering the genomic roots of cancer will provide many new insights into subtypes of disease that are currently lumped together, allowing more precise correlations with prognosis and response to therapy. Perhaps most significantly, these studies are expected to uncover new drug targets that will catalyze the next generation of cancer therapies that will be much more specific and individualized than many current standard approaches. One can therefore anticipate major changes in the approach to diagnosis, prevention and treatment of cancer in the coming years.