Losing genes that help stabilise a cell's DNA may explain why some cancers are resistant to treatment, say scientists. Bowel cancer cells that lost one of three genes displayed unstable chromosomes; a trait that leads to different chromosome numbers within tumour cells and is linked to poor prognosis in patients.
Professor Charles Swanton, who led the study at the Cancer Research UK London Research Institute and University College London Cancer Institute said '... cancers are able to continually shuffle their genetic pack, and deal themselves a better 'genetic hand'. This diversity may help them adapt to new environments, promote tumour spread, or contribute to cancer drug resistance'.
Professor Swanton's team found three genes, previously not known to have a role in maintaining chromosome stability, were crucial for cells to correctly copy their chromosomes during cell division. These genes, located on chromosome region 18q, were often lost in bowel cancer cells. This resulted in abnormally shaped chromosomes, variable numbers of chromosomes and DNA stress.
The researchers showed they could improve the genetic stability of bowel cancer cells lacking these genes by supplying them with an excess of nucleosides, the 'raw materials' needed to build DNA. Cancer cells rapidly divide and make copies of their DNA. An insufficient supply of nucleosides during this process results in DNA errors, which can be beneficial to a tumour.
'By unravelling how this process happens we can now look at turning this strength of cancers into a weakness – too much instability prevents cancer cells from being able to function and ultimately stopping them from working normally, causing them to die. We're now looking for ways in which this process can be targeted in order to tip cancer cells over the edge', said Professor Swanton.
Cancer Research UK chief scientist, Professor Nic Jones, noted that the chromosome region where the three genes in question are found 'is lost in many cancers'. The study's findings may therefore be relevant not only to bowel cancer, but other types of cancer as well.
The study was published in the journal Nature.