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Speeding discovery of the 'human cancer genome'

Two gene discoveries announced in separate reports in the June 30, 2006 issue of Cell highlight one way to speed through the human genome in search of those genes most important for spawning cancer. Both groups say that a critical element in the enterprise to efficiently characterize the "human cancer genome" --a comprehensive collection of the genetic alterations responsible for major cancers--is the strategic comparison of human tumors with those of mice.

As a demonstration of the value of such strategic comparisons between species, the researchers report promising finds: one of the research teams identified two genes that can--in some circumstances--conspire to produce liver cancer, while the second uncovered a gene important to the spread of melanoma, the most serious form of skin cancer. Such functionally important genes, and the larger genetic pathways of which they are a part, are also those with the most promise as potential targets for cancer drugs, according to the researchers.

"With improvements in genome technology, we've found that human cancer is noisy," said Howard Hughes Medical Institute investigator Scott Lowe of Cold Spring Harbor Laboratory. "There are lots of alterations, only some of which causally contribute to the disease."

"Genetically engineered mice, by definition, develop more defined cancers than humans," he said. "Mice can therefore be used as a filter to help reduce that noise, and as a tool to determine, in areas of chromosomal alteration, what changes are functionally relevant."

The difficulty stems from the fact that studies that scan the genomes of human tumors for differences typically find hundreds to thousands of genes that distinguish cancer and noncancer.

Some of those differences are at the root of the cancer, while others are what Lowe refers to as "evolutionary byproducts." In other words, they are genes that simply came along for the ride with those that actual
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Source:Cell Press


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