Breast cancer cells can cut and paste genes from one place to another to create dangerous new combinations of DNA, a Cancer Research UK study reveals1.
For the first time, researchers have identified a particular cut and paste job – known as a chromosome rearrangement – which occurs repeatedly in breast tumours and seems to play an important role in their development.
The rearrangement moves the position of a gene called heregulin, creating hybrid DNA that may have powerful cancer-causing effects. Scientists believe heregulin could be an important target for future anti-cancer drugs.
Scientists funded by Cancer Research UK at the Hutchison/MRC Research Centre, University of Cambridge, collaborated on the study with a team at the Institut Paoli-Calmettes in Marseilles.
Researchers labelled genes with brightly coloured fluorescent dye and noticed that the heregulin gene had been cut from a chromosome (one of the cell’s bundles of genetic material) and in its place another piece of DNA pasted in.
They found the rearrangement in cells from five different breast tumours and two pancreatic tumours, suggesting that it is not just a chance event, but may be playing an important role in cancer’s development.
Cancer Research UK’s Dr Paul Edwards, of the Hutchison/MRC Research Centre, says: “The chromosomes of cancer cells are often unstable and parts of them frequently get swapped around. We can see this by labelling different chromosomes with different colours.
“What we’ve found is that in breast cancer the rearrangement of chromosomes isn’t random, but that a particular rearrangement happens over and over again, suggesting that it plays a key role in the development of the disease.”
In healthy tissue, heregulin plays an important role in encouraging cells to grow and divide. Cutting and pasting the gene to a new position may make it over-active, or make it active in the wrong kind of cell, sending the growth of cancer cells spiralling out of control. Or it could create a hybrid gene, with potent cancer-causing properties.
Dr Edwards adds: “Moving bits of gene around can cause real problems. Understanding how our genes can be mixed around during the development of cancer is crucial if we are to identify new targets for anti-cancer drugs.”
Professor Robert Souhami, Cancer Research UK’s Director of Clinical Research, says: “If a genetic fault happens again and again in cancer, it’s an indication that the fault is making a real contribution to the disease’s development.”
He adds: “Identifying such cancer-causing errors, and working out how they might be contributing to cancer, is an exciting area of research that may bring us new targets for anti-cancer drugs.”
- Genes, Chromosomes and Cancer37 (4) (advanced published online, August 2003)
Chromosomes in cancer cells often get broken and when the bits are rejoined, bits of different chromosomes may get swapped over. Chromosomes are bundles of genes, and sometimes the rejoining sticks parts of two unrelated genes together to create a completely new, dangerous gene, which can cause cells to proliferate.
Heregulin protein is normally made, when needed, by the supporting tissue of the breast as a signal to breast cells to grow. The chromosome rearrangement results in the breast cells making heregulin themselves, causing them to divide at the wrong time.