Sorting the Genetics Puzzle of Breast Cancer:

Sorting the Genetics Puzzle of Breast Cancer: TGen Researcher and collaborators use technology to categorize breast cancers based on DNA Activity

February 24,2003

Sorting the Genetics Puzzle of Breast Cancer: TGen Researcher and collaborators use technology to categorize breast cancers based on DNA Activity

Phoenix, Monday, Feb. 24 Most cases of breast cancer are due to unknown causes. In fact, cancer specialists believe that the condition we call "breast cancer" is actually several different diseases with different origins.

A researcher at the Translational Genomics Research Institute (TGen), along with collaborators at the National Institutes of Health and in Sweden used a new gene chip technology to divide breast cancers into different groups based on their DNA activity. Their findings are reported in the paper Molecular classification of familial non-BRCA1/BRCA breast cancer, which appears in the Mach 4 issue of the Proceedings of the National Academy of Sciences.

This study illustrates perfectly of how the tools stemming from the Human Genome Project are positively effecting cancer research, said Jeffrey M. Trent, Ph.D., TGen president and scientific director, as well as the papers senior author. At TGen, were using those tools to power research and deliver these innovations to the individual patient.

About one in every ten cases of breast cancer runs in families. Several years ago, researchers found two genes, BRCA1 and BRCA2 that cause breast cancer. But those two genes account for only a quarter of familial breast cancers, and researchers have so far been unable to identify additional breast cancer genes.

These non-BRCA1/BRCA2 breast cancers (termed BRCAx) probably comprise a diverse group, meaning that the frequency of genetic change leading to the development of breast cancer may differ in different populations.

"We hope that using this kind of global approach to analyzing complex diseases such as breast cancer will help explain why the cancers develop, with the long-term goal being improved and individualized treatment," said Ingrid A. Hedenfalk, PhD, of Lund University and Malm University Hospital in Sweden, first author of the study.

Gene chips are a relatively new tool for studying the relationship between genes and disease. A chip, also known as a microarray, is a postage-stamp sized glass slide dotted with an orderly array of minuscule dabs of DNA from a particular tissue.

Microarrays can be used to monitor the simultaneous activity of thousands of genes in a single cell such as a breast cancer cell.

Hedenfalk and her colleagues in Sweden, and at the National Human Genome Research Institute in Bethesda, MD, had previously shown that these gene expression patterns were different in cancers caused by abnormalities in the BRCA1 gene compared with cancers caused by mutations in BRCA2. They were able to divide the tumor cells into two different groups based on gene expression profiles.

The researchers have now applied that same technique to BRCAx cancers, the familial breast cancers not caused by mutations in BRCA1 or BRCA2.

"We found that the breast cancers included in our study could be separated into two distinct groups based on differences in their gene expression fingerprints," said Hedenfalk.

The gene chip studies grouped together breast cancer tissue from members of the same family--mother and daughter or two sisters, which suggests that the underlying cause of each family's cancer is hereditary, Hedenfalk pointed out.

"Our findings illustrate the power of profiling. Instead of using the lens of the microscope were now using the lens of genetics to determine where a genetic alteration may occur and further solve the puzzle of breast cancer, noted Hedenfalk.

For Trent, its further evidence that TGens multi-disciplinary approach creates a critical mass across a broad spectrum that is positioned to profoundly affect human health. As the pace of discovery continues to accelerate, TGen is committed to fostering scientific creativity and excellence in disease-focused research.

TGen, located in Phoenix, Arizona, is a research institute whose mission is to make and translate genomic discoveries into advances in human health.

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