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Mapping Cancer's Genetic Makeup

If all the ways genes run amok to cause cancer were laid out in a dictionary, scientists would be able to decipher only a small part of the first page.

Hoping to change that, the government is set to begin a $100 million pilot project to begin unraveling the genetic makeup of cancer, aiming to speed the discovery of culprits and treatments that today is largely a matter of scientific luck.

The Cancer Genome Atlas will "go beyond and behind the front lines and enumerate the complete list of genomic insurgents that lead to cancer," said Dr. Francis Collins, the National Institutes of Health's genetics chief, in announcing the project's first phase Tuesday.

The project will build "a powerful network of researchers, technologies and resources to tackle the cancer problem like it's never been tackled before," he said.

This is a far more complex project than research that mapped the human genome, a molecular blueprint for the human species. But the technology does exist to finally track down the cascade of genetic changes required to spark any of the 200 diseases collectively called cancer — knowledge crucial to develop better treatments, Collins said.

"You remember when people were skeptical that we could determine the genome of just one individual," said Collins, who helped direct that project. To map all the genes involved in cancer, "we're talking about basically thousands of Human Genome Projects."

But, "the time is right," he added. "We have the opportunity, because of advances in technology, to really look at the global nature of what is wrong with the cancer cell in a way that frankly we could not have dreamed of even a few years ago."

Scientists have discovered numerous genes that play a role in cancer. Sometimes a single genetic mutation is enough to spark a tumor, sometimes it just makes people more vulnerable to the disease. Other changes mean the difference between a fast-growing killer or a less dangerous tumor, or determine whether a particular treatment is likely to work.

But developing cancer usually involves about a dozen critical genetic alterations — a domino effect — that differ by malignancy, and scientists have uncovered only a fraction of them.

"There are certain rites of passage for all cancer cells," explained Dr. Ronald DePinho of Harvard Medical School, a leading geneticist who said the new project should significantly speed the hunt for them. "The challenge of cancer is its complexity."

But the payoff can be huge. A handful of so-called targeted drugs — Herceptin, Gleevec, Iressa, Tarceva — are proving remarkably effective at battling certain cancers in patients with specific faulty genes.

That's only a small portion of patients. But those drugs show that "if you can find pivotal mutations, you can actually change clinical practice," said Dr. Anna Barker of the National Cancer Institute.

With The Cancer Genome Atlas — abbreviated, with scientist humor, TCGA to reflect the four "letters" that make up DNA's code — researchers now working independently will come together to hunt not just specific gene mutations, but chromosome rearrangements, faulty on/off switches and other abnormalities. All the data will be made public for use by researchers anywhere in the world.

Funded by the NCI and Collins' National Human Genome Research Institute, it will begin as a three-year pilot project focusing on two or three cancer types that will be chosen within the next few months. Even that smaller first phase will require collecting hundreds of tumor samples from hundreds of patients.

By Lauran Neergard

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