Gene Mutations Show Roles of Sunlight and Smoking in Cancer
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In two new studies, researchers have sequenced the genome and mapped the entire series of thousands of genetic mutations that are not inherited but accumulate in the cells to cause small-cell lung cancer and melanoma.
The results show most of the 23,000 gene mutations associated with small-cell lung cancer are caused by the cocktail of chemicals found in cigarettes.
"On the basis of average estimates, we can say that one mutation is fixed in the genome for every 15 cigarettes smoked," says researcher Peter Campbell, of the Cancer Genome Project at the Wellcome Trust Sanger Institute in Cambridge, England, in a news release.
More than 33,000 gene mutations were associated with melanoma, a rare but deadly form of skin cancer responsible for most skin cancer deaths.
Researchers say ultraviolet (UV)-light-induced gene mutations caused by exposure to sunlight were responsible for the vast majority of these mutations.
"Indeed because of the clarity of the genome data, we can distinguish some of the early, UV-induced mutations from the later mutations that do not have this signature, presumably occurring after the cancer cells spread from the skin to deeper tissues," says Campbell.
"These are the two main cancers in the developed world for which we know the primary exposure," says researcher Mike Stratton, also of the Wellcome Trust Sanger Institute, in the release.
"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," says Stratton.
"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 from ultraviolet radiation," Stratton says."Our cells fight back furiously to repair the damage, but frequently lose that fight."
In the studies, published in Nature, researchers used new DNA sequencing technology to decode the genome of cancerous tissue samples taken from one adult with small-cell lung cancer and another with melanoma and compared it with the genome of normal healthy tissue.
Researchers say the results represent a complete catalog of the genetic changes and mutations that occur on the road to lung cancer and melanoma.
The next step will be to identify which of those gene mutations drive the cells to become cancerous. Then, researchers would be able to develop new drugs to target the specific gene mutations and create individualized treatments based on each patient's cancer genome.
SOURCES: Pleasance, E. Nature, Dec. 16, 2009, advance online edition.
News release, Wellcome Trust Sanger Institute.
News release, Nature Journals.
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