Growth factor receptors, which lie at the head of this pathway, are often found in a deregulated state in many tumors as well. The simplest of these mechanisms are the point mutations that cause the substitution of one DNA base for another. The most widely documented point mutations are those affecting the ras oncogenes. These mutations are found largely in the codons specifying the 12th and 61st amino acid residues of the ras proteins. However, alterations of either of these two codons in the ras proto-oncogene yield proteins that confer special growth advantage on the cells that sustain these mutations, which explains the frequent appearance of these mutations in human tumor cell genomes.
Gene amplification is another frequently found aberration in human tumor cell genomes.
Most autosomal genes are present in two copies per cell. In many human tumors, however, oncogenes may be present in dozens or even hundreds of copies per cell. This amplification is achieved via two distinct mechanisms. These gene copies often distort the normal karyotypic banding pattern of the chromosome in which they are lodged. As a consequence, a homogeneous staining region is observed at a specific site along the chromosome.