This week, scientists have gained an unprecedented insight into the cancer genome – the full range of genes found in cancer cells. Massive experiments looking at almost all the known genes in the human genome have revealed fascinating genetic changes in two of the most lethal human cancers: pancreatic cancer and a type of brain cancer, glioblastoma. The results were published in three papers in the journals Science and Nature. Let’s take a look at them.
The researchers painstakingly scanned the genomes of the cancer cells, searching for small changes in their DNA (‘point mutations’) and for areas where genes had been either deleted or ‘copied and pasted’ next to each other. These are the types of genetic errors that distinguish normal cells from cancerous ones. To test whether these gene changes actually made a difference to the way the cell worked, the researchers also looked for changes in the levels of the proteins that are produced from these genes.
Finding useful patterns in a mass of data
Genes and proteins don’t act alone; many of them work together in production lines, or ‘pathways’, which make things happen in the cell. In these studies, the researchers found that, although hundreds of different genes were altered in the cancers they looked at, the most important ones were all involved with just a few pathways. These pathways were critical to the way cells communicate with each other and respond to the world around them.
In the pancreatic cancer study, the mutated genes fell into just 12 pathways, all of which were faulty in more than two thirds of the tumours they looked at. And some of them were defective in all of their samples.
The individual faulty genes were interesting too. A number of genes were found that had never been associated with brain or pancreatic cancer before. And about half of young people with brain cancer and nearly all of the patients with secondary disease had mutations in one gene that is involved with producing energy in the cell, IDH1.
But what does this all mean?
Of course, if so many different genes could be disrupted in any individual cancer, trying to develop treatments is very difficult, because we have no way of knowing what to target. A drug that replaces or knocks out the function of one gene has only a small chance of working if we don’t know which gene is faulty.
However, because these faulty genes were all involved with just a few key pathways, things become much simpler. Trying to find drugs that fix the function of the pathway as a whole is a better strategy because there is a much smaller range of processes to target. So new research into targeted therapies for these cancers can now focus on fixing the few overall processes that we know are disrupted, and not the hundreds of individual genes.
What can studies like this tell us?
Because of the staggering number of genes in our genome, and the complex way they all interact, looking at the entire genome at once helps us to spot patterns and links between the genes that are often mutated. Studies like this give us a ‘global’ view of the gene changes in cancer cells, so that we can find out more about which processes in the cell drive the development of cancer. Research into single specific genes is still useful, but because genes don’t just work on their own, small studies need to be complemented by large genome-wide studies that give us the whole picture.
Studies like this are slowly giving us a comprehensive picture of the ‘cancer genome’ and exciting insights into the genes and pathways that are disrupted in cancer. They will help us to direct research into new treatments as well as understand the fundamental processes that can make a cell become cancerous.
This was a guest post by our Health Information Officer Jessica Harris.