Cancer genes and the pathways they control.pdfVIP

CELEBRATING OUR TENTH YEAR H I S TO R I C A L P E R S P E C T I V E Cancer genes and the pathways they e n i c i d e control m e r u t a Bert Vogelstein Kenneth W Kinzler n / m o c . e The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last r u t decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely a n . identified, and the pathways through which they act characterized. The purposes of this review are to highlight examples of w w progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation. w / / : p t t h What we know product. Such inactivations arise from missense mutations at p u The cast. Alterations in three types of genes are responsible for residues that are essential for its activity, from mutations that result o r tumorigenesis: oncogenes, tumor-suppressor genes and stability in a truncated protein, from deletions or insertions of various sizes, G g genes Tables 1 and 2 . Unlike diseases such as cystic fibrosis or mus- or from epigenetic silencing. A mutation in a tumor-suppressor n cular dystrophy, wherein mutations in one gene can cause disease, no gene is analogous to a dysfunctional brake in an automobile; the i h s single gene defect ‘causes’ cancer. Mammalian cells have multiple car doesn’t stop even when the driver attempts to engage it. Some i l b safeguards to protect them against the potentially lethal effects of recently described tumor-suppressor genes have been hypothesized u P cancer gene mutations, and only when several genes are defective to exert a selective advantage on a cell when only one allele is inacti- e does an invasive cancer develop. Thus it is best to think of mutated vated and the other remains functional