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Scientists decode set of cancer genes
(Agencies)
Updated: 2008-11-06 11:41 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." Dr. Ley said, "We wanted to start studying a cancer where it would make a difference to people and their families if we could begin to unravel its genetic roots." They chose this particular patient because she was a perfect example of one of the toughest challenges in treating the disease: figuring out early on which patients have a bad prognosis and immediately need the most aggressive therapy, like a bone-marrow transplant. Doctors routinely try to gauge the severity of this leukemia by examining patients' chromosomes, the structures that carry genes. The testing does not examine the DNA itself, but just checks to see if the chromosomes look normal. Certain abnormalities warn of a bad outlook. But some patients whose chromosomes look perfectly fine turn out to have a vicious form of the disease anyway. And that was true of the woman in the study. Her chromosome test was normal, but she still died just two years after the disease was diagnosed, despite a barrage of chemotherapy and two bone-marrow transplants. Had the doctors known her prognosis early in her illness, they would have treated her even more aggressively from the start, Dr. Ley said. Before starting treatment, she had donated samples of bone marrow and skin, so the researchers could compare her normal skin cells to cancer cells from her bone marrow. After she died, her family gave the scientists permission to sequence her entire genome. Dr. Wilson said the family knew that her DNA -- and therefore some of their own as well -- had now become part of history. The family wishes to remain anonymous, Dr. Wilson said. They did not respond to a request for an interview with The New York Times that was passed on to them by the researchers. 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." It will take more research to determine exactly what the mutations do. Researchers would also like to know the order in which they occurred, and whether there was one that finally tipped the balance towards cancer. "When this patient came to the cancer center and had a bone marrow biopsy, she already had 10 mutations," Dr. Wilson said. "You'd love to know, if you had taken a bone marrow sample a year before, what would you have seen?" Tests 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. "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." |
