UCL researchers have revealed how cancers build resistance to treatment through genetic diversity.
Bowel cancer cells missing one of three genes can rapidly reshuffle their genetic ‘pack of cards’ – the chromosomes that hold the cell’s genetic information. This reshuffling has been previously shown to render tumours more resistant to treatment.
Researchers led by Professor Charles Swanton, based at Cancer Research UK’s London Research Institute and the UCL Cancer Institute, have discovered that this genetic ‘card trick’ can be caused by the deletion of three genes found on one particular chromosome, a region known as ‘18q’.
Loss of this region is well-known in bowel cancer and the new findings help shed light on the role it plays.
Professor Swanton said that the genetic design within cancer is complex, and these findings have developed our knowledge of the disease:
“Recent work from Cancer Research UK has shown that the genetic landscape within a cancer is very complex, fundamentally changing our understanding of the disease.
“One explanation behind this is that cancers are able to continually swap bits of chromosomes, potentially helping them adapt to new environments, resulting in tumour spread, or resistance to drugs.
“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 stops 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.”
Normal cells have 46 chromosomes, but in cancer cells this number can constantly change, in a process called Chromosomal Instability. This makes tumour cells incredibly diverse and helps them become resistant to treatments.
When cancer cells grow they must copy their DNA before giving a copy to the two new daughter cells. The researchers found that in bowel cancer cells, part of chromosome 18 is deleted. This results in the loss of three genes that are located in this chromosome and causes problems in DNA copying.
These copying problems then trigger a series of events that lead to incorrect numbers of chromosomes being passed on to daughter cells, causing the chromosomal chaos seen in tumours.
The researchers were able to reduce chromosomal instability by 50 per cent in bowel cancer cells lacking the three genes. They did this by adding the basic building blocks of DNA, namely nucleosides, to the cells, preventing further copying errors from occurring, and the chromosomes from rearranging.
Professor Nic Jones, Cancer Research UK’s chief scientist, said:
“This region of chromosome 18 is lost in many cancers, suggesting this process is not just seen in bowel cancers.
“By piecing together the puzzle of how the same cancer can be so complex and varied means scientists can start looking for ways to prevent this happening in the first place or turning this instability against cancers.”
The research was published in Nature this week.
