What is a translocation?
DNA is powerful but delicate. At only 2 nanometers in diameter (a nanometer is the equivalent of one millionth of a millimeter), it is a fine thread that can snap during the process of cell replication. Each of our cells is equipped with DNA repair machinery, which, when it is working properly, detects and immediately repairs any breaks. But if something goes wrong during this process, the consequences can be disastrous. Under rare circumstances, the repair machinery can accidentally reattach a broken-off piece of DNA to the wrong chromosome. The result is a chromosomal translocation.
When a team of scientists led by researchers at the Broad Institute and elsewhere looked at the genetic landscape of seven prostate cancer tumors, they noticed that the prostate cancer genome was riddled with rearrangements. Many pieces of chromosomes had been broken off and reattached in the wrong places, resulting in deletions, translocations, and the fusion of genes. What caused these initial breaks remains a mystery. Once the damage was done, DNA repair proteins tried to piece the chromosomes back together again, but, like Humpty Dumpty of nursery rhyme fame, the genome could never be completely restored to its original condition, and instead becomes a scrambled version of its former self.
DNA breaks can happen when DNA is damaged by environmental factors, like UV light from the sun, nuclear radiation, or carcinogenic chemicals. Reactive oxygen species – a natural by-product of cellular metabolism – can also cause this kind of damage. Mutations in DNA repair genes can keep proteins from fixing these lesions.
Even if a mistake is not detected and fixed, many translocations are harmless. However, certain rearrangements can be particularly harmful, causing several different kinds of cancer, including some forms of leukemia and Ewing’s sarcoma.
The abundance of genomic rearrangements in the prostate cancer genome raises many questions about how common chromosomal translocations are in cancer. In the prostate cancer study, researchers used a technique called whole genome sequencing to get a comprehensive view of the genome – this is what allowed them to see these global changes. As other kinds of cancers receive the same attention, it will be interesting to see if similar patterns of rearrangements emerge or if prostate cancer is unique in its large number of chromosomal translocations.