Tag Archives: p16

‘Epigenetic’ Gene Tweaks Could Trigger Cancer

You could be forgiven for thinking of cancer as a genetic disease. Sure, we know it can be triggered by things you do – smoking being the classic example – but most of us probably assume that we get cancer because of a genetic mutation – a glitch in our DNA. It turns out that this is not quite the end of the story.

We now have the first direct evidence that switching off certain genes – something that can be caused by our lifestyle or the environment we live in – can trigger tumours, without mutating the DNA itself. The good news is that these changes are, in theory, reversible.

All cells contain the same DNA, but individual genes in any cell can be switched on or off by the addition or subtraction of a methyl group – a process known as epigenetic methylation.

For years, researchers have known that mutations to our DNA – either those passed on at birth or those acquired as a result of exposure to radiation, for example – can cause cancer. But epigenetic changes have also been implicated in cancer because abnormal patterns of gene methylation are seen in virtually all types of human tumours.

For example, a gene called MLH1 produces a protein that repairs DNA damage. It is often mutated in colon cancer tumours, but in some tumour samples the gene is healthy, but appears to have been silenced by methylationThe problem is that it has been difficult to test whether abnormal methylation occurs as a result of a tumour or is a cause of its growth.

In genetics you can easily delete a gene and see what the consequence is, but it’s much harder to direct methylation to specific regions of the genome,” says Lanlan Shen of Baylor College of Medicine in Houston, Texas.

To get round this problem, Shen and her colleagues used a naturally occurring sequence of DNA, which draws in methyl groups to methylate nearby genes. They call it their “methylation magnet”.

The team inserted this sequence next to the tumour suppressor gene, p16, in mouse embryonic stem cells. These embryos then developed into mice that carry the “methylation magnet” in all of their cells. The team focused on methylating p16 because it is abnormally methylated in numerous cancers.

They monitored the rodents for 18 months – until they reached the mouse equivalent of middle age. Over this time, 30 per cent of the mice developed tumours around their body, including in their liver, colon, lungs and spleen. None of a control group of genetically identical mice developed tumours.

Some tissues showed faster methylation than others, for example in the liver, colon and spleen, and that’s exactly where we saw the tumours grow,” says Shen. “It seems like methylation predisposed the tissue to tumour development.” She reckons that methylation silences p16, which lifts the break that it normally places on any abnormal cell division.

Source: https://www.newscientist.com/