Milestone study probes cancer origin

Scientists are reporting a significant milestone for cancer research after charting 21 major mutations behind the vast majority of tumours.

The disruptive changes to the genetic code, reported in Nature, accounted for 97% of the 30 most common cancers.

Finding out what causes the mutations could lead to new treatments. Some causes, such as smoking are known, but more than half are still a mystery.

Cancer Research UK said it was a fascinating and important study.

A tumour starts when one of the building blocks of bodies, a cell, goes wrong. Over the course of a lifetime cells pick up an array of mutations which can eventually transform them into deadly tumours which grow uncontrollably.

The international team of researchers was looking for the causes of those mutations as part of the largest-ever analysis of cancer genomes.

The well-known ones such as UV damage and smoking mutate the DNA, increasing the odds of cancer.

But each also leaves behind a unique hallmark - a piece of "genetic graffiti" - that shows if smoking or UV radiation has mutated the DNA.

Researchers, led by the Wellcome Trust Sanger Institute in the UK, hunted for more examples of "graffiti" in 7,042 samples taken from the 30 most common cancers.

The found that 21 separate "graffiti signatures" could account for 97% of the mutations which led to cancer.

Prof Sir Mike Stratton, the director of the Sanger Institute, told the BBC: "I'm very excited. Hidden within the cancer genome are these patterns, these signatures, which tell us what is actually causing cancer in the first place - that's a major insight to have.

"It is quite a significant achievement for cancer research, this is quite profound. It's taking us into areas of unknown that we didn't know existed before.

"I think this is a major milestone."

Other signatures were related to ageing and the body's immune system. Cells respond to viral infection by activating a class of enzymes which mutate the viruses until they can no longer function.

"We believe that when it does that, there is collateral damage - it mutates its own genome as well and now becomes much more likely to become a cancer cell as it has a huge number of mutations - it's a double-edged sword," said Prof Stratton.

However, 12 of the signatures defy explanation for now.

It is hoped that if some of them can be pinned down to things in the environment then new ways of preventing cancer could be developed.

It may also spur further research. One of the unknown causes of mutation happens only in neuroblastoma, a cancer of nerve cells which normally affects children, so something unique is happening there.

Prof Nic Jones, Cancer Research UK's chief scientist, said: "We know that environmental factors like smoking and overexposure to UV rays can cause faults in DNA which can lead to cancer, but for many cancers we don't know what triggers the faults in our DNA that can lead to cancer mutations.

"The genetic fingerprints identified in this fascinating and important study identify several new processes driving the development of cancer.

"Understanding what's causing them could be an extremely important way to get the bottom of how cancer develops in the first place - and this will lead to new ways to prevent and treat the disease."