• Wed
  • Jul 30, 2014
  • Updated: 11:39pm
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CANCER

British researchers publish first detailed map of genetic faults that cause cancer

Researchers publish first detailed map of genetic faults that cause cancer, which should help in finding cures for the disease

PUBLISHED : Sunday, 18 August, 2013, 12:00am
UPDATED : Sunday, 18 August, 2013, 1:25am

The first detailed map of genetic faults that cause cancers has been published, offering profound insights into the disease.

The map describes more than 20 "genetic signatures", or patterns of mutation, that alone or in combination drive 30 different types of cancer, including brain, lung, pancreas and breast tumours.

Independent cancer specialists who have seen the research said it was "extremely important" and was likely to lead to new strategies to prevent and ultimately treat the disease.

While scientists know, or have a good idea about, the causes of around half of the genetic signatures behind cancers, the rest are a mystery. They may be due to chemicals in the environment, or faults that arise during ageing.

Most cancers are thought to be caused by mutations in DNA, perhaps triggered by chemicals or radiation, which go unrepaired and build up over a person's lifetime. The mutations eventually lead to uncontrolled cell proliferation.

The causes of some cancers are well understood.

Too much ultraviolet (UV) light from the sun's rays causes mutations in skin cells, and if those mutations fall in certain genes in one cell, the cell becomes a cancer. Similarly, the chemicals in tobacco smoke cause mutations in mouth, throat and lung cells, and lead directly to tumours.

"What is remarkable is how little we know about the processes that are causing the mutations in other types of cancer," said Mike Stratton, the lead author on the study and director of the Sanger Institute in Cambridge, England. "That is the question we set out to address."

His team studied more than 7,000 genomes from cancer patients. By comparing the DNA of cancer cells with that of healthy cells in the same patients, they spotted patterns of mutations that arose in common forms of the disease.

In skin cancer, for example, UV light usually caused a mutation in which the letter "C" in the genetic code was changed into a "T". This switch could occur at various locations. Similarly, the most damaging tobacco carcinogens turned a "C" into an "A" to cause lung cancer.

All of the cancers were driven by two or more patterns of mutation, though some were more complex. Some patterns of mutations caused only one type of cancer, for example neuroblastoma in children, but others were common in many forms of the disease. In 25 of the 30 cancers, at least one mutational signature was due to ageing. Another pattern of mutations, caused by the faulty repair of damaged DNA, appeared in pancreatic, ovarian and breast cancers.

The work has shed light on how the body's natural defences might inadvertently drive a range of cancers. When cells are infected by viruses, they can switch on genes that produce a family of enzymes. These enzymes destroy viruses by mutating their DNA, but the onslaught may cause collateral damage. "It's speculation, but it may be that in killing the virus, many mutations are scattered in the genome of the cell itself, and that cell can then go on to become a cancer," Stratton said.

The findings are expected to drive research into the causes of mutations behind each cancer. One way to do this is to expose human cells to suspected carcinogens in the environment to see if they produce similar patterns of mutations. The work could also lead to the development of drugs that mutate cells even further and kill them off in the process.

Ray Waters, head of cancer studies at Cardiff School of Medicine, said the map was a step towards more personalised treatments for cancer. "Cancer medicine is moving away from general therapies that are used on everyone towards knowing what mutations are causing cancer in an individual and what then will be the best therapies to begin with," Waters said.

Nic Jones, chief scientist at British charity Cancer Research UK, 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 ... 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 to the bottom of how cancer develops in the first place, and this will lead to new ways to prevent and treat the disease."

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