Numerous alterations in DNA sequence underlie the development of every neoplasm. These sequence variants can be transmitted through the germline and result in susceptibility to cancer, or can arise by somatic mutation. A central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis (referred to here as 'cancer genes'). Since the advent of recombinant-DNA technology more than two decades ago, there has been considerable success in this enterprise. Following the first report of a somatic mutation in a human cancer gene -the conversion of amino-acid 12 of HRAS from glycine to valine in the human bladder carcinoma cell line T24/EJ 1 -a substantial number of human cancer genes have been identified, and their biological properties have been assiduously investigated. The proteins that are encoded by cancer genes normally regulate cell proliferation, cell differentiation and cell death. Mutations underlying oncogenesis also occur in genes that mediate DNA-repair processes . These result in an increased rate of somatic mutation, which, in turn, might increase the likelihood of a growth-control gene being mutated. We have compiled a list of cancer genes from the published literature. The census illustrates several striking features with respect to the types of sequence alteration, cancer classes in which oncogenic mutations have been identified and protein domains that are encoded by cancer genes.
Criteria for inclusion in the cancer-gene census
*Cancer Genome Project, Human Genome Analysis Group and Pfam Group,