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'Pulverized' chromosomes linked to cancer?
Date:1/19/2012

t isn't, leading to chromosome damage. Second, it is out of sync: the micronucleus keeps trying to replicate its chromosomes long after replication of the other chromosomes was completed. For cell division to be successful, every step of the process must occur in the proper order, at the proper time. In fact, when study co-author Regina Dagher directly analyzed the structure of the late-replicating chromosomes, she found them to be smashed to bits -- exactly what was predicted as the first step in chromothripsis.

The final piece of the puzzle came when Pellman's colleague Neil Ganem, PhD, examined what happens to these pulverized fragments, using an imaging trick that marked the chromosome in the micronucleus with its own color.

"It has been theorized that micronuclei are garbage disposals for chromosomes that the cell doesn't need anymore," Pellman comments. "If that were true, the smashed pieces would be discarded or digested, but we found that, a third of the time, they're donated to one of the daughter cells and therefore cold be incorporated into that cell's genome.

Pellman says that the findings suggest that, unexpectedly, whole chromosome aneuploidy might promote cancer in a very similar way to other kinds of genomic alterations. The key event may be mutations in oncogenes and tumor suppressors. This mechanism may also explain how cancer cells acquire more than one such mutation at a time.

"Although chromothripsis occurs in only a few percent of human cancers, our findings suggest that it might be an extreme instance of a kind of chromosome damage that could be much more common," says Pellman, who adds that accelerating this process in cancer cells, thus generating so many mutations that the cells die, may represent a possible strategy for new therapies against certain tumors.


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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

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