Translocations

Another category of mutations involves alterations of larger amounts of DNA, often at the level of the chromosome. These are called translocations and involve the breakage and movement of chromosome fragments. Often, breaks in two different chromosomes allow for the formation of two 'new' chromosomes, with new combinations of genes.

While it might appear that this would not cause much trouble, since all the genes are still present, the process can lead to deregulated cell growth in a number of ways. The genes may not be transcribed and translated appropriately in their new location. The movement of a gene can lead to an increase or a decrease in its level of transcription. The breakage and rejoining may also occur within a gene (as shown in green above), leading to its inactivation. Translocations are common in leukemias and lymphomas and have been less commonly identified in cancers of solid tissues.

For some cancers, particular translocations are very common and may even be used in diagnosing the disease. An example would be an exchange between chromosomes 9 and 22 seen in over 90% of patients with chronic myelogenous leukemia (CML). The exchange leads to the formation of a shortened form of chromosome 22 called the Philadelphia chromosome (after the location of its discovery). This translocation leads to the formation of an oncogene from the abl proto-oncogene.^{(1) (2)}

Other cancers that are often (or always) associated with particular translocations include Burkitt's lymphoma, B-cell lymphomas and several types of leukemia.

1. Nowell PC, Hungerford DA. "Chromosome studies on normal and leukemic human leukocytes." J Natl Cancer Inst (1960). 25: 85-100.
2. Rowley JD. "A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining." Nature (1973). 243: 290-293. [PUBMED]