For the first time, researchers have decoded all the genes of a person with cancer and found a set of mutations that may have caused the disease or aided its progression.
Using cells donated by a woman in her 50s who died of leukemia, the scientists sequenced all the DNA from her cancer cells and compared it with the DNA from her own normal, healthy skin cells. Then, they zeroed in on 10 mutations that occurred only in the cancer cells, apparently spurring abnormal growth, preventing the cells from suppressing that growth and enabling them to fight off chemotherapy.
The findings will not help patients immediately, but researchers say they could lead to new therapies and will almost certainly help doctors make better choices among existing treatments, based on a more detailed genetic picture of each patient's cancer. Though the research involved leukemia, the same techniques can also be used to study other cancers.
“This is the first of many of these whole cancer genomes to be sequenced,” said Richard Wilson, director of the Genome Sequencing Center at Washington University in St. Louis and the senior author of the study. “They'll give us a whole bunch of clues about what's going on in the DNA when cancer starts to bloom.”
The mutations – genetic mistakes – found in this research were not inborn, but developed later in life, like most mutations that cause cancer. (Only 5 percent to 10 percent of all cancers are thought to be hereditary.)
The new research, by looking at the entire genome – all the DNA – and aiming to find all the mutations involved in a particular cancer, differs markedly from earlier studies, which have searched fewer genes. The project, which took months and cost $1 million, was made possible by recent advances in technology that have made it easier and cheaper to analyze hundreds of millions of DNA snippets. The study is being published Thursday in the journal Nature. Wilson said he hoped that in five to 20 years, decoding a patient's cancer genome would consist of dropping a spot of blood onto a chip that slides into a desktop computer and getting back a report that suggests which drugs will work best.
“That's personalized genomics, personalized medicine in a box,” he said. “It's holy grail sort of stuff, but I think it's not out of the realm of possibility.”
Until now, Wilson said, most work on cancer mutations has focused on just a few hundred genes already suspected of being involved in the disease, not the 20,000 or so genes that make up the full human genome.
The older approach is useful, Wilson said, “but if there are genes mutated that you don't know about or don't expect, you'll miss them.”
Indeed, eight of the 10 mutations his group discovered would not have been found with the more traditional approach.
A cancer expert not involved with the study, Dr. Steven Nimer, chief of the hematology service at Memorial Sloan-Kettering Cancer Center, called the research a “tour de force” and the report “a wonderful paper.” He said the whole-genome approach seemed likely to yield important information about other types of cancer as well as leukemia.