“15 cigarettes equal one DNA mutation” captures graphically the enormity of what was discovered when a UK-led team of scientists reported this week how they cracked the code of two killer cancers: small cell lung cancer and malingnant melanoma. Another compelling revelation was they said they could see “sunlight’s signature” in the DNA mutations of the melanoma cells.

As part of a worldwide push by the International Cancer Genome Consortium to unravel the genomes of cancers of major social and clinical importance around the world, scientists at the Wellcome Trust Sanger Institute in Cambridge, revealed on Wednesday how they found nearly 23,000 mutations in lung cancer cells and over 30,000 in melanoma cells, compared to cells of normal tissue from the same individuals.

Peter Campbell, a haemotologist and cancer-genomics expert at the Sanger Institute, and one of the scientists who worked on both studies and co-authored the papers that appeared this week in Nature, described the vast number of mutations as remarkable, and reflecting on the team’s estimate that a typical smoker acquires one lung cancer mutation for every 15 cigarettes he or she smokes, said:

“Every pack of cigarettes is like a game of Russian roulette.”

“Most of those mutations will land where nothing happens in the genome and won’t do major damage, but every once in a while they’ll hit a cancer gene,” added Campbell, as reported by Nature News.

The researchers also found that the mutations were not distributed evenly in the genome: many were outside the regions that code for genes, and they thought this was probably because cells work harder to repair DNA damage in gene-coding regions.

This is an important insight, and if proven, will help to shed light on some very important questions about the extent to which environment and lifestyle impact DNA: for instance, do carcinogens cause mutations directly (suggesting they are mostly preventable), or does cancer disrupt the DNA repair systems of cells?

The two studies suggest that it is the former, and that these two cancers are indeed largely preventable, because the researchers said they found that most of the DNA changes were traceable to cancer-causing effects of tobacco chemicals in the lung cancer genome and to ultraviolet light in the skin cancer genome.

Another important discovery the team sequencing the lung cancer genome made was that they found one mutation already discovered last year, in CHD7, a gene that controls other genes, appeared again and again, in three independent cells lines, suggesting that targeting recurrent mutations could be a new direction for drug development.

Not everyone is convinced that cancer-genome sequencing is about to transform the way cancer is diagnosed and treated: because it is still very expensive.

This was the view of Steve Elledge, a specialist in DNA damage and cancer genetics from Harvard Medical School in Boston, Massachusetts, who said such an approach won’t be practical until scientists have hundreds of sequences readily available:

“It’s still very expensive, and I think all these efforts should be coupled with an equal amount of effort on studying gene function,” he told Nature News.

Related story: Entire Genomes For Lung And Melanoma Cancers Sequenced By UK Researchers, 16 Dec 09.

Sources: Nature News, Wellcome Trust, MNT Archives.

Written by: Catharine Paddock, PhD