One mutation per 15 cigarettes: genome maps reveal how cancer develops

15 February 2010

Research led by the Wellcome Trust Sanger Institute has revealed for the first time almost all of the mutations in the genomes of two cancers: a malignant melanoma and a lung cancer.

Cancers are caused by mutations in DNA, which are acquired during a person's lifetime. Lung cancer causes around one million deaths worldwide each year and almost all are associated with smoking. The number of mutations found in the genome of the lung cancer cells - almost 23 000 - suggest that a typical smoker would acquire one mutation per 15 cigarettes smoked.

Although malignant melanoma accounts for only 3 per cent of skin cancer cases, it is the cause of three out of four skin cancer deaths. The melanoma genome contained more than 30 000 mutations that carried a record of how and when they occurred during the patient's life.

"These are the two main cancers in the developed world for which we know the primary exposure," said Professor Mike Stratton, from the Cancer Genome Project at the Sanger Institute. "For lung cancer, it is cigarette smoke and for malignant melanoma it is exposure to sunlight. With these genome sequences, we have been able to explore deep into the past of each tumour, uncovering with remarkable clarity the imprints of these environmental mutagens on DNA, which occurred years before the tumour became apparent.

"We can also see the desperate attempts of our genome to defend itself against the damage wreaked by the chemicals in cigarette smoke or the damage fromultraviolet radiation. Our cells fight back furiously to repair the damage, but frequently lose that fight."

"The knowledge we extract over the next few years will have major implications for treatment," said Dr Peter Campbell from the Sanger Institute. "By identifying all the cancer genes we will be able to develop new drugs that target the specific mutated genes and work out which patients will benefit from these novel treatments."

Image: Small-cell lung cancer genome. Credit: Nature (see papers below), © 2009

References

Pleasance ED et al. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 2009;463(7278):184-90.
Pleasance ED et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2009;463(7278):191-96.