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
"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
"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.