Development of cancer is conventionally viewed as a gradual process, taking years to accumulate multiple point mutations and chromosomal rearrangements, and progressing through increasingly malignant phenotypes. New research by a team at the Wellcome Trust Sanger Institute has shown that, in some cases, cancer can result from a single catastrophic event involving tens to hundreds of genomic rearrangements. Using advanced DNA sequencing techniques, the team found that 2-3% of cancer samples, across many common subtypes, had dramatic structural changes affecting highly localised regions of one or more chromosomes that could not be explained using standard models of DNA damage. This type of damage was especially common in bone cancers, where around 25% of samples showed signs of chromosomal crisis.
The team have proposed that such extensive damage is likely to occur when the chromosomes are condensed for mitosis and could be caused by ionising radiation or linked to telomere attrition. If the cell attempts to repair such extensive damage, the evidence suggests that the repair goes badly wrong, resulting in a genome that is riddled with mutations. In most cases, such haphazard repairs would be detrimental to the cell’s ability to survive and divide but in some cases can amplify cancer genes or inactivate tumour suppressor genes. It is remarkable that the cell can not only survive such a cataclysmic event but can emerge with a selective advantage.
The study is published in the journal, Cell.