Although cancer is usually the result of years of erratic mutations, scientists have discovered instances of mutations that arise on a much larger scale than previously thought possible, where entire chromosomes are shattered and glued back together, but shuffled. A study led by Philip J. Stephens (http://dx.doi.org/10.1016/j.cell.2010.11.055) suggests that chromothripsis, which is Greek for shattering chromosomes, occurs as a single event.
This has important consequences, since we typically think of cancer as the gradual accumulation of so-called point mutations and chromosomal aberrations. A point mutation occurs when a single letter of DNA mutates into another. Although there are 3 billion letters in a single DNA molecule, point mutations alone are sometimes important contributors to disease. We only need to consider sickle-cell anemia patients, whose red blood cells have unusual shapes due to a change in a single letter of their DNA. Another way in which DNA is modified is by chromosomal abberations, where segments of DNA are deleted, inverted, moved to other regions, or duplicated.
But why do such mutations cause cancer? Aren't there mechanisms that prevent cells from replicating uncontrollably? There are two major kinds of genes that act as protection mechanisms: proto-oncogenes and tumor-suppressor genes. A great way of visualizing their roles is to use a car analogy: The proto-oncogenes form the gas pedal since they encourage cells to replicate, whereas tumor-suppressor genes form the brake pedal, since they inhibit replication. In a nutshell, mutations cause our car to break down: When proto-oncogenes undergo mutations, the gas pedal no longer works and we can no longer stop the cells from replicating. Conversely, if tumor-supressor genes become dysfunctional due to mutations, the brake pedal stops working and cell division once again cannot be stopped.

Dr. Stephens and his colleagues believe that chromosome shattering occurs while the cell is replicating. Although they remain unsure of what exactly causes the shattering, they speculate that it might be due to a pulse of ionizing radiation, but further studies are needed to confirm this hypothesis. As with all new scientific discoveries, it is perhaps too early to be certain of its impact. Regardless, it offers us a clearer understanding of the mechanisms of cancer. And if we are to improve diagnostic tools and treatments, this is but a first step in the right direction.
Given that 2011 is the International Year of Chemistry, it should come as no surprise that scientists are increasingly eager to better grasp the molecular basis of cancer
