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Small number of cancers may be caused by 'one-off onslaught', study suggests

24 January 2011
Appeared in BioNews 592

UK scientists have shown that a single, catastrophic event can induce multiple cancer-causing mutations, simultaneously. The event was first discovered when analysing the genome of a leukaemia patient and subsequently detected in a range of other cancers. This finding challenges the widely-held view that cancer is caused by the gradual accumulation of several mutations over time.

'The first patient was a chance finding and we didn't know what to make of it', said Dr Peter Campbell of the University of Cambridge, who led the study. The genomes of over 700 cancer cell lines were screened and similar catastrophic events were identified in two to three percent of cases. This was true across a variety of cancers, with bone cancer showing a higher prevalence of roughly 25 percent.

Normally when a chromosome suffers such severe damage it becomes fragmented and the cell dies. The current study showed that in a small number of cases the cells were able to survive by piecing back together the fragmented chromosome, in a process the authors of the study termed 'chromothripsis'. This process is error prone and as a result the cell acquires several genetic mutations in one go. These mutations significantly accelerate the progression towards a cancerous state.

'Faced with hundreds of DNA breaks, the cell's DNA repair machinery attempts to rescue the genome. The resultant hodgepodge bears little resemblance to its original structure, and the genomic disruption has wholesale and potentially oncogenic effects', said Dr Campbell.

Current efforts are geared towards understanding what causes 'chromothripsis'. It is speculated that ionising radiation, such as x-rays and environmental radiation, may contribute.

The study was published in the journal Cell.

SOURCES & REFERENCES
Cancer genetics: One catastrophe, many mutations
Nature |  13 January 2011
Humpty Dumpty chromosomes fast-track cancer
New Scientist |  16 January 2011
Sequencing Study Suggests Single Large Rearrangement Events Underlie Some Cancers
Genome web |  6 January 2011
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