Gene Findings Boost Breast Cancer Research

Scientists find new DNA driving malignancy, and a host of implicated proteins

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HealthDay Reporter

THURSDAY, May 24, 2007 (HealthDay News) -- Four new studies released Thursday are shedding new light on the genetics of breast cancer, especially for one of the best-known breast cancer genes, BRCA1.

"The more we can understand the underlying mechanism for BRCA1, the better shot we have at developing chemoprevention" for women who carry the DNA mutation, said one expert, Kathleen Malone, a cancer epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle.

She was not involved in the studies, which were all published in the May 25 issue of Science.

In one article, scientists who track how the body repairs its DNA (the "DNA damage response") when it is exposed to chemicals or other carcinogens say they've found a possible new breast cancer gene.

The new candidate gene is called Rap80, according to a partnership of scientists at the Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, and the Dana-Farber Cancer Institute, Boston.

Rap80 is a protein that is crucial for BRCA1 to do its repair work properly, they found.

It has long been known that certain mutations in the BRCA1 and BRCA2 gene prevent it from doing normal repair work. This puts carriers of the gene defect at dramatically higher risk of breast and ovarian cancers.

Yet, mutations in these genes explain less than 50 percent of inherited cancers, the scientists from Penn and Dana-Farber said.

Rap80 deficits may help explain many other cancer cases, the scientists said. If BRCA1 is mutated, it can't bind to the RAP80 protein, the scientists found. If this DNA damage is not identified and fixed, the mutations can lead to malignancy.

Other researchers found that the list of proteins involved in the DNA damage response is much longer than believed.

"A lot more proteins are called into action than we ever guessed," said Stephen Elledge, the Gregor Mendel Professor of Genetics and of Medicine at Harvard Medical School and an author on two of the four papers.

"The list of proteins totals 700," Elledge said. "Before, we knew about 20 proteins." The discoveries, he said, "will give us a higher-resolution picture of what the BRCA1 gene is doing inside the cells."

"Cells constantly have a problem with DNA, with cells breaking down," explained Elledge. "Cells have a built in sensory network to find out if there is a problem. If you can't fix the problem, it could lead to mutation and cancer."

"The hope is that as we learn enough about BRCA1, we can figure out what it isn't doing and try to fix that," Elledge added. The list of proteins gives scientists a large database to hunt for other potential cancer genes.

Malone called the host of papers "an amazing convergence" of new findings from different laboratories.

With the identification of the role of Rap80, Malone agreed that "we could be talking about another breast cancer candidate gene."

In a Science perspective accompanying the papers, John H. J. Petrini, a researcher at Memorial Sloan-Kettering Cancer Center, noted that the new research "brings fundamental new information to the table, while at the same time reminding us that the more we know, the more complicated things get."

More information

To learn more about the BRCA1 gene, visit the U.S. National Human Genome Research Institute.

SOURCES: Stephen Elledge, Ph.D., Gregor Mendel Professor of Genetics, Harvard Medical School, Boston; Kathleen Malone, Ph.D., cancer epidemiologist, Fred Hutchinson Cancer Research Center, Seattle; May 24, 2007, University of Pennsylvania, press release; May 25, 2007, Science

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