Somatic Evolution in Cancer - Somatic Evolution in Progression - Clonal Expansions

Clonal Expansions

One common feature of neoplastic progression is the expansion of a clone with a genetic or epigenetic alteration. This may be a matter of chance, but is more likely due to the expanding clone having a competitive advantage (either a reproductive or survival advantage) over other cells in the tissue. Since clones often have many genetic and epigenetic alterations in their genomes, it is often not clear which of those alterations cause a reproductive or survival advantage and which other alterations are simply hitchhikers or passenger mutations (see Glossary below) on the clonal expansion.

Clonal expansions are most often associated with the loss of the p53 (TP53) or p16 (CDKN2A/INK4a) tumor suppressor genes. In lung cancer, a clone with a p53 mutation was observed to have spread over the surface of one entire lung and into the other lung. In bladder cancer, clones with loss of p16 were observed to have spread over the entire surface of the bladder. Likewise, large expansions of clones with loss of p16 have been observed in the oral cavity and in Barrett's esophagus. Clonal expansions associated with inactivation of p53 have also appear in skin, Barrett's esophagus, brain, and kidney. Further clonal expansions have been observed in the stomach, bladder, colon, lung, hematopoietic (blood) cells, and prostate.

These clonal expansions are important for at least two reasons. First, they generate a large target population of mutant cells and so increase the probability that the multiple mutations necessary to cause cancer will be acquired within that clone. Second, in at least one case, the size of the clone with loss of p53 has been associated with an increased risk of a pre-malignant tumor becoming cancerous. It is thought that the process of developing cancer involves successive waves of clonal expansions within the tumor.

Read more about this topic:  Somatic Evolution In Cancer, Somatic Evolution in Progression

Other articles related to "clonal expansions":

Somatic Evolution In Cancer - History - Knudson, Cairns, and Nowell
... in some tumor suppressor genes, including CDKN2A (p16), predispose to clonal expansions that encompass large numbers of crypts in some conditions such as ... advantageous mutations arise that lead to clonal expansions ... Since 1976, researchers have identified clonal expansions and genetic heterogeneity within many different types of neoplasms ...