New progress has been made on the road to understanding the origins of genetic changes in tumour cells. The prevalent theory has been that genetic changes in tumour cells come about in multiple stages over a long time. However, a recent study by researchers at Lund University shows that this does not have to be the case at all, but that the cancer cells instead can be subject to several major chromosomal changes at the same time.

By filming cancer cells as they grow, the researchers discovered that tumour cells can undergo a special form of division that is not seen in healthy cells.

The results are presented in the scientific journal PNAS. Behind the study are researcher and doctor David Gisselsson Nord and colleagues in his research group.

“We have long known that changes in the genetic make-up of body cells play a part in the development of tumours. However, we don’t know a lot about how the genetic changes in the tumour cells actually come about. Above all, it has been difficult to understand why many tumour 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”, says David Gisselsson Nord.

The research group’s findings mean new and important knowledge of how such chromosome damage can arise. By filming cancer cells as they grow over a long period of time, they discovered that tumour cells can undergo a special form of division. Normal cells divide in two opposite directions and we already know that tumour cells sometimes divide towards three poles.

“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”, says David Gisselsson Nord.

“These major, simultaneous chromosome changes could explain why tumours in young children, which have not had very long to grow, can demonstrate comprehensive changes in genetic make-up”, he says.

The study, which has been carried out in close collaboration with the newly started Lund company PHI AB, was performed on cells from a type of cancer known as Wilms’ tumour – a disease that generally affects children of pre-school age.

It has not been possible to carry out a study of this type until now because it has previously been difficult to film living cells in detail over a long time without exposing the cells to harmful fluorescent light. As an alternative, the researchers in this study used digital holographic microscopy, a novel technique by which cells are exposed only to weak laser light for very limited time periods.

Both the research group in Lund and other groups have previously shown that a high proportion of abnormal cell divisions of the type that they have now studied are linked to a higher risk of children with Wilms’ tumour dying of the disease.

“Now we can more easily understand why this is the case, because it is believed that an accumulation of cells with mutually different genetic make-up within a tumour means that they respond less well to chemotherapy. But this is still only a theory”, says David Gisselsson Nord.

It is hoped that this type of cell division can be used in some way as a target for cancer treatment, but the research is complicated and a lot of work remains to be done.

“At the moment, the most important thing is to wait for our findings to be confirmed by other studies”, says David Gisselsson Nord.


Source: Lund University

The article ‘Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis’ in PNAS, www.pnas.org/.

http://www.pnas.org/content/early/2010/11/05/1006829107.abstract?sid=8fbe1c7a-13d2-4f9e-9a89-d908fbf44306



Full bibliographic information:

Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis. David Gisselssona, Yuesheng Jina, David Lindgrenc, Johan Perssond, Lennart Gisselssond, Sandra Hankse, Daniel Sehica, Linda Holmquist Mengelbiera, Ingrid Øraf,Nazneen Rahmane, Fredrik Mertensa, Felix Mitelmana, and Nils Mandahla. Published online before print November 8, 2010, doi: 10.1073/pnas.1006829107 PNAS November 8, 2010