Breast Cancer Gene Requires ATM Gene To Function Properly

The breast-cancer gene BRCAl cannot repair DNA damage without a gene called ATM (ataxia telengiectasia mutated).

Scientists at Baylor College of Medicine and Howard Hughes Medical Institute (HHMI) report a direct link between the two genes in the Nov. 5 issue of the journal Science. Their findings offer clues about the molecular chain of events that leads to breast cancer.

Both BRCAl and ATM are called tumor-suppressor genes. They normally function to repair damage to DNA, the two spiraling strands of chemical building blocks that encode the body's genetic blueprint.

Mutations in BRCA1 lead to breast cancer. Mutations in ATM result in a disease called ataxia telengiectasia (AT). AT is characterized by the loss of particular brain cells and motor control and the development of cancers during young adulthood.

Usually when double strands of DNA are broken by radiation or other causes, BRCAl is turned on to repair the genetic damage. Researchers have known that this process is regulated by another gene, but they didn't know which one until now.

Dr. Stephen Elledge and colleagues found that when BRCAl was mutated so that ATM could no longer turn it on, BRCAl was unable to function.

"Our study places two important tumor suppressors in a single cancer pathway," says Dr. Elledge, a Baylor professor of biochemistry and an HHMI investigator. "Our findings suggest that defects in this single pathway might be responsible for a significant percentage of all breast cancer."

Other researchers have suggested that people with a mutation in one ATM gene are predisposed to breast cancer and might increase that risk by exposing themselves to X-ray-based mammograms. Dr. Elledge's findings might help explain the molecular basis for such a disposition, but those claims need to be substantiated by clinical studies, he says. As many as one in 100 women are thought to have one mutant ATM gene.

Dr. Elledge's coauthors on the Science paper are Dr. David Cortez, Yi Wang and Dr. Jun Qin.

The research was supported by the National Institutes of Health, the American Cancer Society, The Jane Coffin Childs Memorial Fund for Medical Research and the L.E. Gordy Cancer Research Fund.

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©2006 Texas Medical Center

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