Scientists Decode Set of Cancer Genes

For the first time, researchers have decoded all the genes of a person with cancer and found a set of mutations that might 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 to 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 would 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 K. 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.Dr. Wilson said he hoped that in 5 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.Wilson“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, Dr. 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, Dr. Wilson said, “but if there are genes mutated that you don’t know about or don’t expect, you’ll miss them.”Indeed, 8 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.” Dr. Nimer said the whole-genome approach seemed likely to yield important information about other types of cancer as well as leukemia.“It is supporting evidence for the idea that you can’t just go after the things you know about,” Dr. Nimer said.He added, “It would be nice to have this kind information on every patient we treat.”NimeDr. Nimer also predicted that oncologists would quickly want to start looking for these mutations in their patients or in stored samples from former patients, to see if they could help in predicting the course of the disease or selecting treatments.Nimer,Studying cancer genomes has become a major thrust of research. In the past few years the government has spent $100 million dollars for genome studies in lung and ovarian cancers and glioblastoma multiforme, a type of brain tumor. The person who gave her cells for the study at Washington University became not only the first cancer patient, but also the first woman to have her entire genome decoded. Her information will be available only to scientists and not posted publicly, to protect her privacy and that of her family. The only other complete human genomes open to researchers so far have come from men, two scientists known for ego as well as intellect, who ran decoding projects and chose to bare their own DNA to the world: James D. Watson and J. Craig Venter. Their genomes are available for all to inspect.The woman at Washington University had acute myelogenous leukemia, a fast-growing cancer that affects about 13,000 people a year in the United States and kills 8,800. Its cause is not well understood. Like most cancers, it is thought to begin in a single cell, with a mutation that is not present at birth but that occurs later for some unknown reason. Generally, one mutation is not enough to cause cancer; the disease does not develop until other mutations occur.Most of them are just these random events in the universe that add up to something horrible,” said Dr. Timothy J. Ley, a hematologist at Washington University and the director of the study.The researchers chose to study this disease because it is severe and the treatment has not improved in decades.It’s one of the nastiest forms of leukemia,” Dr. Wilson said. “It’s very aggressive. It affects mostly adults, and there’s really no good treatment for it. A very large fraction of the patients eventually will die from their disease.”WilsonBefore starting treatment, the patient they studied had donated samples of bone marrow and skin, so the researchers could compare her normal skin cells to cancer cells from her bone marrow. Some of the patient’s mutated genes appeared to promote cancer growth. One probably made the cancer drug-resistant by enabling the tumor cells to pump chemotherapy drugs right out of the cell before they could do their work. The other mutated genes seemed to be tumor suppressors, the body’s natural defense against dangerous genetic mistakes.Their job is surveillance,” Dr. Wilson said. “If cells start to do something out of control, these genes are there to shut it down. When we find three or four suppressors inactivated, it’s almost like tumor has systematically started to knock out that surveillance mechanism. That makes it tougher to kill. It gets a little freaky. This is unscientific, but we say, gee, it looks like the tumor has a mind of its own, it knows what genes it has to take out to be successful. It’s amazing.”WilsonTests of 187 other patients with acute myelogenous leukemia found that none had the eight new mutations found in the first patient.。That finding suggests that many genetic detours can lead to the same awful destination, and that many more genomes must be studied, but it does not mean that every patient will need his or her own individual drug, Dr. Wilson said.Wilson“Ultimately, one signal tells the cell to grow, grow, grow,” he said. “There has to be something in common. It’s that commonality we’ll find that will tell us what treatment will be the most powerful.”