Thursday, 24 February 2011

When catastrophe strikes a cancer cell

Jose M. C. Tubio & Xavier Estivill

How do the mutations that lead to cancer come about? The traditional view is that a gradual process involving continual acquisition of heritable genetic changes by cells causes cancer. There is, however, an alternative view that single catastrophic events can lead to multiple mutations. In a paper published in Cell, Stephens et al. provide evidence for the concept of catastrophism in cancer.

The authors coin the term chromothripsis (from ‘chromo’, for chromosome; and ‘thripsis’, for breaking into small pieces) to designate this phenomenon.

Stephens and colleagues combined next-generation sequencing and single nucleotide polymorphism (SNP) array data to analyse the patterns of somatic (non-germline) genomic rearrangements in tumours. Intriguingly, they found that in some cases the changes consist of tens to hundreds of rearrangements, confined to one or a few chromosomes.

Rearrangements are common in cancer, so how can the authors tell whether such mutations were caused by a single event? They argue that the final configuration of the rearrangements they observed could be explained only by a single catastrophic episode, rather than by a series of independent events. Rearrangements due to chromothripsis are usually restricted to a few chromosomes, within which breakpoints show a non-random distribution.

The potential implications of chromothripsis as a cause and/or mediator of cancer are evident. As Stephens et al. point out, the generation of so many rearrangements in a single genomic crisis makes it likely that more than one cancer-causing lesion would occur.

Read more in Nature

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