Cancer as a disease of genetic alterations

The major discovery in cancer biology has been that tumorigenesis is a multistep process associated with accumulated genetic alterations in somatic cells. The progression of a tumour through preneoplasia to frank neoplasia and then invasion and metastasis is the result of successive rounds of clonal expansion of somatic cells that acquire a selective growth advantage as a result of mutations in genes that control cellular proliferation and death.1 Mutations result either in the activation of oncogenes, which promote cellular proliferation or inhibit cell death, or in the inactivation of tumour suppressor genes, which inhibit proliferation or promote cell death. To become a cancer cell, a normal cell needs to accumulate at least five or six of these mutations.1

Mutations occur at a higher rate in cancer cells because their genetic material (chromosomes or DNA) is intrinsically unstable.1 This genetic instability seems to be a “property” of cancer cells.1

Colorectal carcinoma is the best studied example of the genetic alterations that underlie human cancer.2 A normal mucosal cell with inactivation of a tumour suppressor gene called APC …