Chromosome catastrophe theory: an introduction to “chromothripsis”

According to a new paper in the journal Cell, researchers at the Sanger Institute at Cambridge, in England, believe they have discovered a completely new mechanism for the initial development of about 2 or 3 percent of all cancers.

The dominant theory of cancer development is based on the gradual accumulation of so-called “point mutations” and rearrangements of parts of a chromosome, which can occur during the normal replication of DNA that occurs when cells divide to form new cells (mitosis). Some forms of cancer can result from a single point mutation, but prostate cancer (just as an example) is widely believed to require several such mutations over time.

Stephens et al. have now described an utterly different process through which a chromosome in a cell may (almost literally) “explode” into hundreds of fragments. They are calling this “chromothripsis.”

Most of the time, when this happens, that cell is unable to replicate, and dies. However, it appears clear that sometimes the cell is able to knit most or all of the pieces of the DNA back together in a completely new order … and the cell manages to survive and replicate. When such a cell does manage to survive and replicate, it may include one or more transformations in the DNA that induce different types of cancer.

There is a nice article about this work in the New York Times for readers who want to learn more. Clearly, this finding will generate a great deal more research in the future. At present it is utterly unclear why such sudden destruction of an individual chromosome might occur (background radiation events, cell condensation during mitosis, who knows?).

One additional finding may help to provide some short-term insights. Apparently the types of cancer in which this finding is most common are “bone cancers” (by which we assume the authors are implying primary cancers to bone rather than the type of cancer that occurs in the bones of patients with advanced prostate cancer, which are the consequence of metastasis).

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