Digital Holographic Microscopy Reveals How Cancer Cells Gain Extra Chromosomes

Cell biologists have used digital holographic microscopy to show how abnormal distribution of chromosomes takes place in some types of cancer cells.

Investigators at Lund University (Sweden) used Wilms' tumor as a model for cancers with trisomies. They made movies of the tumor cells growing in culture. To prevent damage to the cells during photography, they employed digital holographic microscopy, a novel technique by which the cells were exposed only to weak laser light for very limited time periods.

Results published in the November 8, 2010, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) contrasted with the popular theory that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. Instead, results of the current study showed that trisomic cells could form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeded in a regular fashion, but cytokinesis failure nevertheless led to an asymmetrical segregation of chromosomes into two daughter cells.

"We were even more surprised to see that two of the three poles often fused together to form one daughter cell. This daughter cell thus got extra copies of one or more chromosomes. When we continued to film the cells it emerged that they could continue to divide, and they thus gave rise to new cancer cells with a chromosome set that was different from the original cell,” said first author Dr. David Gisselsson Nord, associate professor of pathology at the Lund University.

"We have long known that changes in the genetic make-up of body cells play a part in the development of tumors. However, we do not know a lot about how the genetic changes in the tumor cells actually come about. Above all, it has been difficult to understand why many tumor cells contain extra copies of one or more chromosomes, despite the fact that this is the most common type of chromosome abnormality in cancer cells,” said Dr. Nord.

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