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Rigged to explode?
Date:1/19/2012

An inherited mutation in a gene known as the guardian of the genome is likely the link between exploding chromosomes and some particularly aggressive types of cancer, scientists at the European Molecular Biology Laboratory (EMBL), the German Cancer Research Centre (DKFZ) and the University Hospital, all in Heidelberg, Germany, have discovered. Their study, published online today in Cell, also presents the first whole genome sequence of a paediatric tumour: medulloblastoma, a brain cancer which is the second most common cause of childhood mortality in developed countries, where only car accidents cause more deaths in children.

Looking at the complete genome sequence of these tumours, the scientists found one or two chromosomes in each cell had countless parts in the wrong order, were missing some genes, and had extra copies of others. Such extensive rearrangements suggested that those chromosomes had been shattered, like a bead necklace that is pulled too hard, and then wrongly reassembled. But the scientists only found these telltale signs of chromosome explosion, or chromothripsis, in samples from a specific group of patients.

"All patients who had inherited a mutation in the TP53 gene showed signs of chromothripsis in their tumour cells, but none of the patients with normal TP53 did" says Jan Korbel, who led the genomics research at EMBL, "so this mutation must be involved either in shattering chromosomes, or in preventing the cell from reacting when a chromosome shatters."

This strong link between the hereditary TP53 mutation and chromothripsis has implications for diagnosis and treatment.

"As clinicians, if we find evidence of chromothripsis in a medulloblastoma sample, we can now look for an inherited mutation in the TP53 gene" says Stefan Pfister, who led the work at the DKFZ, "and we know that any family members who also have the mutation should be screened regularly, as they'll have a very high risk of developi
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Contact: Sonia Furtado Neves
sonia.furtado@embl.de
European Molecular Biology Laboratory
Source:Eurekalert  

Page: 1 2 3

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