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Rigged to explode?
Date:1/19/2012

ng particular types of cancer, including brain tumours."

Cancer treatments often involve killing the tumour cells by damaging their DNA with chemo- or radiotherapy, but these treatments also affect healthy cells in the surrounding tissue. If those cells have healthy copies of p53 the protein encoded by TP53 this gene will monitor the genome, and if it finds too much damage it will instruct the cells to stop dividing, sending them into the cellular equivalent of old age (senescence) or suicide (apoptosis). But if a patient has inherited the TP53 mutation from their parents, all their cells will have faulty copies of this gene, including the cells surrounding the tumour. Thus, those healthy cells will have trouble dealing with the DNA damage caused by such treatments, and could become cancerous themselves. So the findings have immediate clinical implications in that such patients should not be given DNA-damaging chemotherapy or high-dose radiotherapy, since both would greatly increase the likelihood of secondary cancers.

The scientists believe that the TP53 mutation may also play a role in causing chromosomes to shatter in the first place, by shortening telomeres, the caps that keep chromosome ends from fraying. This could make arms from different chromosomes more likely to get stuck to each other and shatter if they're pulled in different directions. Since telomeres naturally shorten with age, this could explain why, when the German scientists expanded their study to another cancer an aggressive form of leukaemia in adults they found that patients who had both a non-inherited TP53 mutation and evidence of chromothripsis were typically of an advanced age.

"Chromothripsis is thought to cause two to three percent of all human cancers," says Korbel, "so if we can really prove how the TP53 mutation affects this process, it could have a big impact on our understanding of how healthy cells in the body turn into tumours."

The study was u
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Contact: Sonia Furtado Neves
sonia.furtado@embl.de
European Molecular Biology Laboratory
Source:Eurekalert  

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