September 25, 2002

Function of Breast Cancer Gene Discovered

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50,000 Americans will die of breast cancer this year, and another 200,000 will be diagnosed with the disease according to the World Health Organization. However, the results of a recent study are providing scientists with better clues into the origin of this deadly illness.

The function of BRCA2, the gene first linked to the development of breast and ovarian cancers in 1995, has been successfully identified by a group of researchers at New York’s Memorial Sloan-Kettering Cancer Center.

Mutations in BRCA2 and its sister gene BRCA1 are responsible for about half of hereditary cases of breast cancer.

“It was known that the gene is involved in DNA repair but exactly how was not clear. Our findings show that it binds directly to the DNA and recruits other molecules to repair damage,” said Haijuan Yang, grad, lead author of the study.

The findings, published in Science magazine, show that BRCA2 performs the functions of a tumor suppresser gene. When in proper working order, it fixes damaged sections of DNA and prevents that damage from causing cancerous mutations in the cell.

The gene was previously believed to have played only an indirect role in this process. When an individual has a faulty version of the gene, those mutations go unchecked which leads to a greater susceptibility to the disease.

Visualizing the gene was the key to the discovery.

“They found a way to make BRCA2 crystallize and used x-ray crystallography to determine its structure. From looking at the various features, they saw that BRCA2 binds directly to DNA,” said Prof. Andrew Yen, pathology, whose research focuses on tumor suppresser genes.

Scientists hope that the research will one day lead to better, targeted cancer treatments.

“One day, it may be possible to use gene therapy to introduce a healthy gene to replace the dysfunctional one, but since BRCA2 is so large it will be very difficult to insert,” Yang said.

Testing for a defective version of the gene is already available for women with a family history of the disease.

“Since the gene is very closely related to the occurrence of breast cancer, those at high risk can undergo routine genetic screening to determine if they should exercise heightened surveillance,” Yen said. While this approach enables prevention but not cure, the work does promise to open new avenues of cancer research.

“Our findings don’t reveal any obvious treatment strategies, but as with all basic science, studying how a process works, and how it malfunctions in cancer brings us closer to understanding the process of tumorigenesis,” stated Nikola Pavletich, principle investigator for the project, in a statement from Howard Hughes Medical Institute.

“We will have to see how people use this information to develop clever research strategies,” Yang said.

The three-year study, sponsored in part by the National Institutes of Health, was a collaboration between the Sloan-Kettering Cancer Center and the University of Texas.

While not a cure, this research places scientists one rung higher on the ladder to understanding a form of cancer that affects one in eight women over the span of a lifetime.

Archived article by Philip Lane