Genome instability

Usually, all cells in an individual in a given species (plant or animal) show a constant number of chromosomes, which constitute what is known as the karyotype defining this species (see also List of number of chromosomes of various organisms), although some species present a very high karyotypic variability.

Sometimes, in a species with a stable karyotype, random variations that modify the normal number of chromosomes may be observed. In other cases, there are structural alterations (chromosomal translocations, deletions ...) that modify the standard chromosomal complement. In these cases, it is indicated that the affected organism presents genome instability (sometimes, it is named genetic instability, or even chromosomic instability). The process of genome instability often leads to a situation of aneuploidy, in which the cells present a chromosomic number that is either higher or lower than the normal complement for the species.

Cellular DNA integrity is often compromised in cancer, and this situation can lead to instability of the cellular genome. Genome instability can refer to the accumulation of extra copies of DNA or chromosomes, chromosomal translocations, chromosomal inversions, chromosome deletions, single-strand breaks in DNA, double-strand breaks in DNA, the intercalation of foreign substances into the DNA double helix, or any abnormal changes in DNA tertiary structure that can cause either the loss of DNA, or the misexpression of genes. Situations of genome instability (as well as aneuploidy) are common in cancer cells, and they are considered a "trademark" for these cells.

It is currently accepted that sporadic tumors (non-familial ones) are originated due to the accumulation of several genetic errors. Any genetic lesion increasing the mutation rate will have as a consequence an increase in the adquisition of new mutations, increasing then the probability to develop a tumor. During the process of tumorogenesis, it is known that diploid cells acquire mutations in genes responsible for maintaining genome integrity (caretaker genes), as well as in genes that are directly controlling cellular proliferation  (gatekeeper genes). Genetic instability can originate due to individual mutations on a specific gene, or due to loss or gain of chromosomes, or, what seems to be more frequent, due to large scale chromosomal reorganizations. Losing genetic stability will favour tumor development, because it favours the generation of mutants that can be selected by the environment.