Cancer is fundamentally a genetic disorder, arising from somatic mutations in multiple genes that affect cell division and proliferation. If one or more mutations are inherited, then fewer additional mutations are required for cancer to develop.
A mutation that allows a cell to divide rapidly provides the cell with a growth advantage; that cell gives rise to a clone of cells having the same mutation. Within this clone, other mutations occur that provide additional growth advantages, and cells with these additional mutations become dominant in the clone. In this way, the clone evolves.
Environmental factors play an important role in the development of many cancers by increasing the rate of somatic mutations.
Oncogenes are dominant mutated copies of normal genes (proto-
The cell cycle is controlled by cyclins and cyclin-
Defects in DNA-
Mutations in sequences that regulate telomerase allow cells to divide indefinitely, contributing to cancer progression. Tumor progression is also affected by mutations in genes that promote vascularization and the spread of tumors.
Epigenetic changes are frequently associated with cancer.
Colorectal cancer offers a model system for understanding tumor progression in humans. Initial mutations stimulate cell division, leading to a small benign polyp. Additional mutations allow the polyp to enlarge, invade the muscle layer of the gut, and eventually spread to other sites. Mutations in particular genes affect different stages of this progression.
Some cancers are associated with specific chromosome mutations, including chromosome deletions, inversions, and translocations. Mutations in some genes cause or allow the missegregation of chromosomes, leading to aneuploidy that can contribute to cancer.
Viruses are associated with some cancers; they contribute to cell proliferation by mutating and rearranging host genes or by altering the expression of host genes.