GENETIC NEWS

Researchers Find Breast Cancer Gene, Spur Hope for New Drugs
Researchers discovered a gene involved in the spread of breast cancer, which may lead to new treatments for a disease that kills about 1 in 35 women.

The gene, called metadherin, may be crucial to cancer’s spread because it helps tumor cells stick to blood vessels in distant organs, researchers at Princeton University and the Cancer Institute of New Jersey found. The gene also makes tumors more resistant to drugs used to wipe out deadly cells.

Breast cancer is the most frequently diagnosed malignancy in U.S. women, excluding cancer of the skin, according to the American Cancer Society. Determining the genetic mechanism involved in the disease’s spread, known as metastasis, may help answer one of the biggest mysteries in cancer research.

“Inhibiting this gene in breast cancer patients will simultaneously achieve two important goals -- reduce the chance of recurrence and, at the same time, decrease the risk of metastatic dissemination,” Yibin Kang, an assistant professor of molecular biology at Princeton who led the research, said in a statement on the Cancer Institute’s Web site. “These are the two major reasons why breast cancer patients die from the disease.”

The finding, published today in Cancer Cell, is based on three years of work, using an approach that combines the emerging science of integrative genomics with the classical methods of clinical research and laboratory experiments, the authors said.

Quick Spread

Breast cancer is caused by a malignant tumor that develops from cells in the breast. The most common sign of breast cancer is a new lump or mass in the breast. Scientists once thought that breast cancer spread first to nearby tissue and underarm lymph nodes before reaching other parts of the body. They now believe cancer cells may break away from the primary tumor in the breast even when the disease is in an early stage.

After re-analyzing clinical breast cancer databases and tumor samples collected from patients, the researchers found an area of human chromosome 8 called 8q22 is repeated multiple times in the genomes of potentially lethal breast tumors. Most normal DNA sequences contain only two copies of a given gene, conveyed from the genomes of the male and female parents.

The researchers went on to discover that among a handful of genes in the 8q22 region, metadherin, also known as MTDH, is responsible for the aggressive behavior of some tumors. The scientists found that tumors which over-express MTDH are more likely to spread to the lungs, other vital organs and bones. These tumors were also found to be more resistant to some chemotherapy agents.

“By analyzing 250 breast tumor samples from patients, we found that this gene is amplified and over-expressed in over 30 to 40 percent of breast cancer cases,” Kang said. “This indicates that new drugs against metadherin may potentially benefit a large population of breast cancer patients.”

The work was funded by a Department of Defense Era of Hope Scholar Award and grants from the National Institutes of Health, the American Cancer Society, the Susan G. Komen Foundation and the New Jersey Commission on Cancer Research.