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Database on mutations should aid cancer fight

Gene map hailed as crucial tool

Washington — The National Institutes of Health announced a plan Tuesday to identify genetic mutations linked to human tumors, research that officials said would give Americans hope of not having to die of cancer.

By mapping genes in hundreds of samples of cancerous tissue, NIH officials said it would be possible to identify combinations of mutations associated with specific types of cancers.

That will allow development of faster diagnostic tools and precise, targeted drugs that they said would be far more effective than current therapies.

As cancer-related mutations are identified and mapped, the information will be placed in a public database, available free to researchers, said Francis Collins, director of the National Human Genome Research Institute.

"This is truly a historic day for cancer patients," said Anna Barker, deputy director of the National Cancer Institute. "I think this is a revolutionary project. It is a turning point in biomedical research. It is a turning point in medicine. It is a turning point in cancer research."

She said she believed discoveries from the systematic genetic analyses might appear soon enough to help some people now struggling with the disease.

"Our purpose today is to begin to turn the fear of cancer — actually Americans' greatest fear — into a future not only free of fear, but filled with hope and the expectation of not having to die of a disease like cancer," said the cancer institute's director, Andrew C. von Eschenbach.

One of every two American men and one of every three women develop cancer.

The cancer institute and the genome institute will spend $50 million each during the next three years on a pilot project to demonstrate the feasibility of mapping genes associated with cancer, officials said.

They said the program would concentrate on the genetic makeup of a handful of cancer types — possibly as few as two or three — that are still to be determined.

"More than 300 genes have been implicated in the diabolical transformation of normal cells into cancer cells, and that has led to major insights into cause, prevention, diagnosis, treatment and cure," said Collins, of the genome institute.

"But we are still working with an incomplete atlas," he added. "It is time to bring the full power of genomics to bear on the problem of cancer."

Although cancer experts believed as recently as 40 years ago that genetic factors were not involved in cancer, they now know that mutations play a central role. More than 200 different types of cancer have been identified, and each may involve scores of unique mutations, experts say.

This realization, and the successful identification of specific mutant genes involved in certain cancers, has led to the development of several drugs, such as Herceptin for some forms of breast cancer and Iressa for some lung cancers.

But these drugs are not effective for many cancer victims, probably because other genetic mutations also underlie the growth of cancer.

In fact, as many as 100 genetic aberrations may be involved in a single cancer, said Harvard University cancer geneticist Ronald DePinho.

Years of effort by teams of investigators have resulted in identifying only five to 15 mutations for any given tumor type, and it is "clear that we are dealing with the tip of the iceberg," he said.

The project has been named "the Cancer Genome Atlas," a designation Collins said was chosen partly because its initials, TCGA, are the same letters used for the chemicals that make up DNA, the genetic code of humans and all other life.

Collins said the project would be more complex than mapping the human genome, a feat his agency and a private organization, the Institute for Genomic Research, announced jointly in 2002.

To reduce the complexity, initial work will concentrate on regions of the human genome known to be associated with cancer, the NIH said.