New studies have unpicked the genetic codes of two cancers, but it's only part of the story. Claire O'Connellreports
IT HAS been heralded as a “fundamental moment” in cancer research: earlier this month scientists announced they had worked out the full genetic sequence of two individual cancers.
Their results catalogue thousands of changes, or mutations, in the DNA of cancer cells compared with normal, healthy cells in the body.
Decoding the cancer “genome” can help us understand how the disease develops and will hopefully help pave the way to better diagnosis and treatment.
The approach is ongoing, with several centres around the world working out what genes have had their sequence of information or “letters” altered in cancer cells.
But the sense of occasion was palpable when these latest results were published online by the high-impact scientific journal Nature.
Prof Mike Stratton from the Cancer Genome Project at the Wellcome Trust Sanger Institute, whose team worked on the studies with researchers from the UK, the US and the Netherlands, spoke animatedly to the BBC.
“This is a fundamental moment in cancer research. From here on in we will think about cancer in a very different way,” he said. “We know that all cancers are due to abnormalities in DNA . . . which are present in the cancer but not in any of the normal cells of the body. Today for the first time in two individual cancers, a melanoma and a lung cancer, we have provided the complete list of abnormalities in DNA in each of those two cancers.”
By trawling through the DNA of cancerous cells and comparing them with corresponding healthy cells, the researchers discovered more than 33,000 mutations in a malignant melanoma skin cancer, and just shy of 23,000 mutations in lung cancer cells.
Their search found evidence of DNA changes going back years, long before the cancer became apparent. The malignant melanoma bore the hallmarks of UV damage, while the lung cancer cells revealed complex signatures of tobacco exposure.
A separate study from the same stable also highlighted shuffling, copying and deletion of DNA sequences in 24 breast cancer samples and was published in print in Natureon Christmas Eve.
But while decoding cancer genomes can provide important information, it’s an achievement that needs to be seen in context, according to Ray Stallings, professor of cancer genetics at the Royal College of Surgeons in Ireland and programme leader of cancer genetics at the Children’s Research Centre in Crumlin.
“There already has been a huge amount of work done on the cancer genome – more than 400 cancer-causing genes have already been discovered. And there are at least 50 different types of cancer being studied by DNA analysis worldwide, so undoubtedly a great amount of information is going to come out of it, but it’s only part of the story,” he says.
“There are many other things that are important in cancer apart from changes in the DNA sequence – there are also what we call epigenetic changes.”
Those epigenetic changes can include the DNA being tagged to determine how genes are switched on or off and changes in the levels or activities of other molecules in the cell that control how genes are expressed.
And of the thousands of actual DNA mutations revealed by the melanoma and lung cancer catalogues published this month, most will not be that important to the cancer itself, adds Stallings.
“The vast majority seen in these studies are totally meaningless, they are just passive events, the DNA is being damaged and the enzymes that are involved in DNA repair are unable to repair it.”
That said, sifting through the genome findings will help in the quest to further pinpoint key mutations in particular cancers, and that information could be useful for looking at those genes in patients and tailoring treatments to suit individuals, he notes. But for now, such expensive large-scale sequences are what he terms “discovery tools”.
While the complexity of changes in cancer cells may seem overwhelming, even on the basis of DNA mutations alone, Stallings explains that understanding the molecular changes that drive cancer opens up more opportunities to intervene.
“Even though there are so many genes that have gone wrong, the identification of one key gene could lead to a new treatment regimen,” he says, citing the case of chronic myeloid leukaemia (CML), where research previously showed that the condition develops through two genes becoming abnormally spliced and generating a troublesome protein.
A drug – Glivec – which can block that protein’s actions, has meant most patients with CML can now manage the condition effectively, he explains. “This is a model that cancer researchers aspire to, where a drug was developed.”
But to get a better sense of the whole picture of what happens in cancer we need to look not just at the DNA sequences, but how the genes are affected in practice.
“It’s a complex series of events and it really would be wrong to focus too heavily on any particular mechanism because there are multiple mechanisms that interact,” says Stallings. “So this is basically one piece of the story, it’s not the total story.”
