ABSTRACT
The selection in tumors operates over many generations of cells, but all within the lifetime of a single host individual. Specific point mutations in RAS genes are frequently found in cells from a variety of tumors including colon, lung, breast, and bladder cancers. The best-known example of activation by a translocation that creates a novel chimeric gene is the Philadelphia chromosome. An early landmark in the people understanding of tumor suppressor genes was Knudson's work in 1971 on retinoblastoma. Compared to adult cancers, embryonal tumors show strikingly little evidence of the usual extensive genetic instability. Tumor suppressor genes may be silenced by deletion (reflected in loss of heterozygosity) or by point mutations, but a very common third mechanism is methylation of the promoter. The people's new understanding of driver mutations in cancer has stimulated an intense effort to develop agents to target the specific molecules or pathways that drive tumor development.
