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Cancer Cells More Likely to Genetically Mutate

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When cells become cancerous, they also become 100 times more likely to genetically mutate than regular cells, researchers have found.

The findings may explain why cells in a tumor have so many genetic mutations, but could also be bad news for cancer treatments that target a particular gene controlling cancer malignancy.

The research was led by Dr. Lawrence Loeb, professor of pathology and biochemistry at the University of Washington School of Medicine  in Seattle. Loeb presented his research at the meeting of the American Association for the Advancement of Science in San Francisco.

Most types of cancer are believed to begin with a random genetic mutation that makes a normal cell go horribly away. This is followed by mutations, which endow the cancer cells with properties allowing them to grow without normal controls to become a tumor. These mutated genes would be targets for chemotherapy.

But Loeb had another idea that he originally hatched many years ago - what if the cancer cells changed somehow, and became much more likely to mutate? These "mutator" cells would develop dangerous genetic mutations at a much faster rate than normal cells, which might account for the high number of mutations seen in tumor cells.

Since the technology of cancer genetics has dramatically improved, Loeb and his colleagues have only recently been able to test this hypothesis. They found that tumor tissue had random mutation rates up to 100 times higher than normal tissue from the same patient. The mutator hypothesis seems to be correct.

Now for the bad news: if cancer cells do indeed become mutator cells, traditional chemotherapy and other drugs may never be very effective against advanced tumors.

"This is very bad news, because it means that cancer cells in a tumor will have mutations that protect them from therapeutics," Loeb explained.

Loeb believes this research may eventually help physicians determine the stage and malignancy of a tumor by testing the number of its mutations. The more mutations, the further along the tumor may be in its development to malignancy or metastasis.

Loeb's work may also lead to a discovery of why cancer cells are becoming mutator cells. If scientists understand what happens in a cancer cell that makes it become a mutator, they might be able to prevent that from happening in other cells, or slow down the mutation rate.

"The idea is that if you might normally get exposed to something in the environment at 20 years old that would give you cancer by age 55, then if we cut the mutation rate in half, you might not get cancer until age 90, and you may even die of something else before that," Loeb explained.