Cancer gene map heralds new era of personalised treatment
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Personalised cancer treatment that will slash the mortality rate of the world’s second-biggest killer is within reach after scientists unveiled a comprehensive catalogue of the disease’s genetic make-up.
An international collaboration involving 1,300 scientists has completed a decade-long project to map the many mutations that drive cancer’s development. The results were published in a series of papers in Nature and its sister journals.
“For more than 30 cancers we now know what specific genetic changes are likely to happen and when these are likely to take place,” said Peter Van Loo of the Francis Crick Institute in London, one of the project leaders. “Unlocking these patterns means it should now be possible to develop new diagnostic tests that pick up signs of cancer much earlier.”
The Pan-Cancer Project read the DNA sequences in 2,600 samples of 38 types of cancer and compared them with the genomes of healthy tissue in the same patients. By tracking the way the 3bn biochemical letters differ between tumours and normal tissues, the researchers can catalogue all the biological pathways involved in cancer.
“This work is helping to answer a longstanding medical difficulty: why two patients with what appear to be the same cancer can have very different outcomes to the same drug treatment,” said Peter Campbell of the Wellcome Sanger Institute, another project leader. “We show that the reasons for these different behaviours are written in the DNA.”
He continued: “The genome of each patient’s cancer is unique, but there are a finite set of recurring patterns, so with large enough studies we can identify all these patterns to optimise diagnosis and treatment.”
In the catalogue, the researchers divided cancer mutations into “drivers” and “passengers”. The vast majority of mutations are passengers, which give the tumour little evolutionary benefit. A small number of driver mutations, typically four or five, make it grow. They range from changes in single letters of genetic code to large-scale rearrangements of chromosomes.
“It is quite surprising that almost all have the same number of driver mutations,” said Jakob Skou Pedersen, a professor at Aarhus University in Denmark. “However, it is consistent with theories that a cancerous tumour needs to change a certain number of mechanisms in the cell before things start to go wrong.”
The mapping project also developed a new method for “carbon dating” the origins of cancer tumours. They were able to identify early mutations in cells that occurred years or decades before cancer appears — possibly opening a window for detection well ahead of any symptoms.
Dr Campbell looked forward to a time, within a few years, when the cancer genome of a patient receiving treatment “will have been sequenced and the doctor will match it against a knowledge bank of cancer genomes to work out the best treatment for the patient”.
Cancer is by far the biggest field of medical research, with about 36 per cent of all pharmaceuticals funding devoted to oncology. Although significant strides have been made in treating the disease, it still kills about 10m people year around the world, the biggest killer after heart disease.
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