Scientists have reconstructed the biological history of two types of cancer in a genetic tour de force that promises to transform medical treatment of the disease.
The
feat, a world first, lays bare every genetic mutation the patients have
acquired over their lifetimes that eventually caused healthy cells in
their bodies to turn into tumours.
The procedure gives doctors a
profound insight into the biological causes of a patient's cancer and
marks a major milestone in progress towards personalised anticancer
therapies and strategies to prevent the disease.
"This is a
really fundamental moment in the history of cancer research. We have
never seen cancer revealed in this way before," said Mike Stratton, a
co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute near Cambridge.
The researchers took diseased cells from a 45-year-old man with a type of skin cancer called malignant melanoma, and from a 55-year-old man with small cell lung cancer.
They then used advanced genetic sequencing machines to read the full
genomes of both the cancer cells and healthy tissues taken from the
same patients.
By comparing the genetic makeup of the diseased
and healthy cells, the scientists created catalogues of all the
mutations found only in the cancerous tissues. Most of these genetic
glitches are harmless, but every once in a while a mutation causes
major damage that pushes a cell closer to becoming cancerous.
The
scientists focused on skin and lung cancer because the environmental
causes are well known. Most melanomas are triggered by overexposure to
ultraviolet rays in sunlight as a child, while almost all small cell
lung cancer is caused by smoking.
In the case of the lung cancer patient,
scientists discovered 23,000 mutations that were exclusive to the
diseased cells. Almost all were caused by the 60 or so chemicals in
cigarette smoke that stick to DNA and deform it. "We can say that one
mutation is fixed in the genome for every 15 cigarettes smoked," said
Peter Campbell, who led the lung cancer part of the study. "That is
frightening because many people smoke a packet a day."
Lung
cancer accounts for one in seven deaths in the UK and is almost
untreatable. Fewer than 10% of patients in the UK survive more than
five years after being diagnosed. The risk of developing the disease
falls dramatically in smokers who have quit for more than 10 years.
Genetic sequencing of the skin cancer cells revealed 33,000 mutations caused by exposure to direct sunlight.
Humans
have 23 pairs of chromosomes that carry all of our genetic material in
the form of three billion pairs of letters. In both patients,
scientists saw a variety of mutations. The most common were point
mutations, which flip one letter of the genetic code into another. More
complex mutations involved missing or extra sequences of DNA.
Occasionally, chromosomes had broken apart or fused together in the
wrong way.
"It's like doing archaeological excavation. You've got
traces and imprints of all these processes that have been operative for
decades before the cancer arose," said Stratton. The work is reported
in two studies published in the journal Nature.
The
rapid advance of genetic technology is likely to make the technique a
routine procedure for cancer patients within 10 years. The Sanger
Institute scientists costed the procedure at $100,000 per person a few
months ago, but they expect that to fall to $20,000 in the next 18
months.
"In the long term, every cancer patient will have this
done in a clinically relevant timeframe, so in the six weeks it takes
to be seen, biopsied and taken into the clinic," said Stratton.
The
research is the first to emerge from a global consortium that is
analysing the genetic makeup of 50 different types of cancer. The
10-year project will help cancer specialists unravel the particular
mutations that drive each variety of tumour.
By understanding the
genetic flaws behind common cancers, scientists hope to develop more
powerful and precise anti-cancer drugs. In the near term, researchers
expect to develop blood tests that pick up signs that a cancer is
returning in patients who have already had surgery or chemotherapy.
By: Ian Sample for 
.