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'Pulverized' chromosomes may be behind cancer

London, Sun, 22 Jan 2012 ANI

London, Jan 22 (ANI): Scientists have apparently found evidence which suggests that micronuclei - present in cancer cells - could potentially disrupt the chromosomes within them, and thus help in triggering disease-causing gene mutations.

 

The findings by Dana-Farber Cancer Institute researchers may point to vulnerability in cancer cells that could be attacked by new therapies.

 

"The most common genetic change in cancer is the presence of an incorrect number of intact chromosomes within cancer cells - a condition known as aneuploidy," said Dana-Farber's David Pellman, MD, the study's senior author.

 

Whole chromosomes can end up outside the nucleus as a result of a glitch in cell division. In normal division, a cell duplicates its chromosomes and dispatches them to the newly forming daughter cells: the original set to one daughter, the twin set to the other.

 

For a variety of reasons, the chromosomes sometimes aren't allocated evenly - one daughter receives an extra one, the other is short one.

 

Unlike the rest of the chromosomes, these stragglers sometimes don't make it to the nucleus. Instead, they're marooned elsewhere within the cell and become wrapped in their own membrane, forming a micronucleus.

 

"We found that cancer cells generated from cells with micronuclei also have a great deal of chromosome breakage," Pellman explained.

 

But researchers didn't know if this was a sign of connection or of coincidence.

 

A vital clue came from a recently discovered phenomenon called "chromothripsis," in which one chromosome of a cancer cell shows massive amounts of breakage and rearrangement, while the remainder of the genome is largely intact.

 

"That finding leapt off the page of these studies-that such extensive damage could be limited to a single chromosome or single arm of a chromosome," Pellman said.

 

"We wondered if the physical isolation of chromosomes in micronuclei could explain this kind of highly localized chromosome damage."

 

To find out, Karen Crasta, PhD, of Pellman's lab and the study's lead author, used a confocal microscope to observe dividing cells with micronuclei. She found that while micronuclei do form duplicate copies of their chromosomes, the process is bungled in two respects. First, it is inefficient: part of the chromosome is replicated and part 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.

 

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 colour.

 

"It has been theorized that micronuclei are garbage disposals for chromosomes that the cell doesn't need anymore," Pellman commented.

 

"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 added.

 

The study has been published in the journal Nature. (ANI)

 


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