Seeking silent genes

Brain Tumour UK and the Samantha Dickson Brain Tumour Trust have been funding this work led by Professor Bill Farrell. 

Cancers are often blamed on ‘mutant genes’ that are raging out of control. But in the last few years the researchfield of ‘epigenetics’ has discovered that some cancers arise becausea gene that controls an important process has been ‘silenced’ from outside, in a process called methylation.

Professor Bill Farrell from the University of Keele explains: “This mechanism is effectively throwing a blanket over the gene. If the silenced gene is supposed to be telling other cells not to divide, they just carry on multiplying and a tumour is born. 'The really exciting thing about genes that have been silenced is that it should be possible to reverse the methylation process and switch them back on,' says Bill.

So far, so good. But which genes have been silenced and which need to be switched on? With PhD student Kevin Dudley, Bill examined laboratory tumours that grow in culture. Using these tumours is not ideal, but since human tumours don’t grow in the lab it’s the only way to start. And the results were very promising: 'Initially, we found 68 genes that were switched off in these pituitary tumours,' explains Bill.

He’s particularly interested intumours in the pituitary gland in the brain because “Pituitary tumours accountfor between 10% and 15% of all brain cancers and about one third invade other parts of the brain and, despite surgical removal, recur. So I’m looking for epigenetic errors that trigger this process.”Having narrowed down the field to 68 genes, the next challenge was toidentify which ones were important.

Some, for example, might simply determine the colour of your eyes and have nothing to do with cancer. So Bill examined five of these genes in a retrospective study ofpituitary cancers in people. “It turned out that a significant proportion of human pituitary tumours also didn’t express these genes in the way that a normal human pituitary would. For two of them, we were able to show an epigenetic aberration. So the laboratory model was successful – it did predict what happens in humans.”

What does this mean for braintumour patients? Bill now hopes that it will be possible to classify brain tumours by their genetic make-up. This will allow surgeons to take samples and determine how dangerous – or not – the tumour is. If we can then switch the silenced genes back on, their job might beto stop cancer cells spreading into other parts of the brain.

Other switched on genes might make dangerous cells more vulnerable to drug treatments. Epigenetic treatments are already becoming available for cancers such as leukaemia, so their potential forthe future is very exciting.