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Similar Cancers Have Different Genetic Profiles
Similar Cancers Have Different Genetic Profiles
Article date: 2001/03/05
BRCA1 and BRCA2 gene mutations can both lead to breast and ovarian cancer, but the genetic profiles of the cancers themselves are strikingly different, according to a study in the New England Journal of Medicine (Vol. 344, No. 8). Researchers expect this new information will prove enormously helpful in identifying new genes involved in cancer and may someday help them develop more effective treatments.

An international team of researchers, led by scientists at the National Institutes of Health, compared the genetic profiles of breast cancers from three groups of women: those with mutations, or mistakes, in the BRCA1 gene, those with BRCA2 gene mutations, and those without mutations of either gene. Inherited mutations in either of these genes are associated with an increased risk for breast and ovarian cancer.

Heredity May Determine Profile

What they found was surprising. Despite the fact that both BRCA1 and BRCA2 cause breast cancer, the breast cancers in women with inherited mutations of these genes had very distinctive genetic profiles.

Doctors have known for years that even though BRCA1 and BRCA2 mutations cause the same type of cancers, the breast cancers these women develop often look and behave very differently. For example, women with inherited BRCA2 mutations usually develop breast cancers that are estrogen receptor-positive (meaning they often respond well to hormonal therapy) but women with inherited BRCA1 mutations usually have estrogen receptor-negative cancers. These differences mean that BRCA1 and BRCA2 tumors probably follow different molecular pathways in their development.

As tumors develop, more and more genes become altered. This leads to inappropriate gene activity, such as protective genes being turned off when they should be on, or increased activity of genes that allow the cell to divide.

Microarray: An Exciting New Technique

The researchers used an exciting new technique called microarray analysis to compare gene activity in BRCA1- and BRCA2-related breast cancers. Microarrays are a kind of genetic catalog containing thousands of genes. Genetic material from a patient's tumor can be examined to take an inventory of which genes are active and which are turned off. The genes in question may have already been implicated in cancer, but chances are, this method will lead to the discovery of many new cancer genes.

"I suspect that, at this level of detail, researchers can see what we have begun to suspect all along ? that every person has a slightly different disease from everyone else," says Dawn Willis, PhD, director of research promotion and communication at the American Cancer Society. "What the microarray makes possible is the identification of all of these unknown genetic targets that can subsequently be sequenced, and their function identified. Then we could design inhibitors just for that specific target molecule."

Profiling Tumors May Improve Treatment

As researchers learn to better characterize specific tumors, cancer treatments are expected to eventually improve.

Doctors already recognize that cancers may respond differently to chemotherapy depending on which genes are active in them. In an editorial comment on the study , Todd R. Golub, MD, of Harvard Medical School asserts that evaluating how well a new drug works could be greatly enhanced when scientists can study its effect on all the genes in the body. In patients with lymphoma, for instance, using microarrays to individually profile each tumor (from the biopsy sample obtained at diagnosis) can help predict the response to chemotherapy.

The fledgling microarray technology is currently for research use only. However, it's possible that in the future it may be used in a clinical setting to profile a patient's cancer and individually design the most effective treatment.


ACS News Center stories are provided as a source of cancer-related news and are not intended to be used as press releases.
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