A Virginia Bioinformatics Institute (VBI) at Virginia Tech researcher, in collaboration with those from other institutions, has discovered a new genetic biomarker that signals a heightened risk for developing breast cancer.
Harold "Skip" Garner, executive director of the VBI, along with Michael Skinner, M.D., professor of pediatric surgery at the University of Texas Southwestern Medical Center, and Dr. James Mullet, a radiologist at Carilion Clinic's Breast Care Center, have found the new genetic biomarker within the non-coding, or "junk," DNA in humans.
Most of our DNA is non-coding, which means that it’s not transcribed into protein. The greatest quantity of non-coding DNA consists of microsatellites, which are specific repeated sequences of one to six nucleotides in the genome. Within the human genome, there are over two million microsatellites where only some have been previously linked to disease.
"We've become increasingly aware that non-coded DNA has an important function related to human disease," said Skinner. "Replication of this study in another set of patients is needed, but the results indicate that this particular gene is an important one in breast cancer and they reveal more details about the expression of the gene. This kind of work could eventually result in the creation of a drug that would specifically interact with this gene to return expression levels to a normal range."
What Garner and his fellow researchers discovered was that longer DNA sequences of a repeating microsatellite were found more often in patients with breast cancer as oppose to healthy volunteers. Between five and 21 copies of the specific repeated DNA sequence can be found in the control, or promoter, region of the receptor gamma (ERR-y) gene, and it was discovered that those with more than 13 copies have a heightened cancer susceptibility rate than those who have less than 13 copies. The increased risk for those with more than 13 copies is about three times higher than those who do not.
Garner and his team of researchers discovered this by using about 500 patient and volunteer samples to sequence a particular region of the ERR-y gene.
"Creating robust biomarkers to detect disease in their early stages requires access to a large number of clinical samples for analysis," said Garner. "The success of this work hinged on collaborations with clinicians with available samples, as well as researchers with expertise in a variety of areas and access to the latest technology.
"We are now working to translate this biomarker into the clinical setting as a way to inform doctors and patients about breast cancer susceptibility, development and progression. Akin to the major breast cancer biomarkers BRCA1 and BRCA2, this will be of particular benefit to those high-risk patients with a history of cancer in their family."
But Garner and his team are not the only researchers investigating breast cancer risk and biomarkers. A team from the Biodesign Institute at Arizona State University has found a panel of 28 biomarkers that has the potential to help diagnose breast cancer earlier than ever. They discovered the biomarkers by studying the crossroad between the body's immune system and cancer. They found, as previous studies have suggested, that proteins created by cancers can prompt the body to make antibodies not found in healthy human beings. These antibodies are called "autoantibodies," and they can be measured in the blood and used to reveal the presence "of a hidden cancer." In addition, protein microarray technology called Nucleic Acid Programmable Array was used to distinguish which antibodies are specific for breast cancer.
Calculating risk and developing biomarkers for the early detection of breast cancer could save lives and lead to novel technology for screening patients affordably and quickly. But more time and research is needed before crossing that threshold.
"There is a big gap between what is suspected and what is known about the genetics of cancer," said Garner. "While more work is needed to better understand how these changes play a role in cancer, these results can be used now as a new test for breast cancer susceptibility and, as our data suggests, for colon cancer susceptibility and possibly other types of cancer. We think this is just the beginning of what there is to be found in our junk DNA."
This study was published in Breast Cancer Research and Treatment.