How Cancer Forms: Scientists Witness Translocation in Living Cells

Cancer can develop in a variety of ways, but one way it can form is through chromosome abnormality. Now, for the first time scientists have directly witnessed the events that lead to the formation of a chromosome abnormality called a translocation. The findings could allow researchers to better understand how and why cancer develops and could allow them to create better treatments for the disease.

Chromosomes are thread-like structures inside cells that carry genes and function in heredity. Human chromosomes each contain a single piece of DNA, with the genes arranged in a linear fashion along its length. When a translocation occurs, though, part of a chromosome breaks off and becomes attached to another chromosome. These chromosome translocations can be found in almost all cancer cells, and it's long been known that translocations play a role in cancer development.

In order to learn a bit more about how translocations form, the researchers created an experimental system in which they induced, in a controlled fashion, breaks in the DNA of different chromosomes in living cells. Using imaging technology, they then watched as the broken ends of the chromosomes reattached correctly or incorrectly inside the cells.

So what did they find? It turns out that translocations can occur within hours of DNA breaks. Their formation is also independent of when the breaks happen during the cell division cycle. While cells have built-in repair mechanisms that can fix most DNA breaks, translocations still occasionally occur.

In order to explore this phenomenon a bit further, the scientists then inhibited key components of the DNA damage response machinery within cells and monitored the effects on the repair of DNA breaks and translocation formation. In the end, the researchers found that inhibition of one component of DNA damage response machinery, a protein called DNAPK-kinase, increased the occurrence of translocations almost by 10-fold.

"These observations have allowed us to formulate a time and space framework for elucidating the mechanisms involved in the formation of chromosome translocations," said Vassilis Roukos, lead scientists of the new study, in a news release.

The findings could allow researchers to better understand the process of cancer formation. In addition, it could lead to novel new treatments that could help prevent translocation.

The findings are published in the journal Science.

Want to learn more about the findings? Check out the video below, courtesy of YouTube.