New Biomarker Identified as Cause of Breast Cancer and Early Indicator

    Researchers at the Medical College of Georgia and Georgia Cancer Center within Augusta University have identified a gene, previously known for its role in DNA repair pathways, which they describe as being a cause of breast cancer. However, due the GT198 gene’s newly identified role in carcinogenesis, it has a strong potential both as a way to diagnose breast cancer early and as a new therapeutic target.

    Previous work has shown that mutations in the gene have been found in early-onset breast and ovarian cancer. Yet now, scientists have shown that progenitor cells, which should ultimately make healthy breast tissue, can also have GT198 mutations, ultimately creating an environment that is highly conducive for the initiation of breast cancer.

    “This gene mutation can be in both the blood and the tumor tissue of patients, and when in the tissue, it’s in high percentages,” explained senior study author Lan Ko, M.D., Ph.D., adjunct associate professor of pathology at the Medical College of Georgia. “We believe that once this gene is mutated, it induces the tumor to grow.”

    The investigators utilized an international sampling of 254 breast cancer cases in both pre- and postmenopausal women. The findings from this study were published recently in The American Journal of Pathology in an article entitled “GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer.”

    Normally, GT198, which acts as a co-activator of receptors for steroid hormones such as estrogen, is normally regulated by estrogen. However, once the gene becomes mutated, GT198 can enable tumor production without estrogen, resulting in classic rapid growth of cancer. “Regardless of how much hormone you have, it’s out-of-control growth,” noted Dr. Ko.

    In this new study, the authors show that GT198 also directly affects stem cells found in blood vessels that make these various components of breast tissue—providing valuable information to scientists to help explain how different tissue layers become tumorigenic.

    “It’s a new target in cancer, and it’s very exciting,” remarked study co-author Nita Maihle, Ph.D., associate director of education and professor of pathology at GRU Cancer Center. “This tells you that all the different types of stromal cells in breast tissue are affected by the GT198 mutation because they all come from a common progenitor cell.”

    The net effect is a cancerous environment filled with cells that feed the various tumor layers with a continued supply of mutant cells.

    “Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198,” the authors wrote. “These findings imply the presence of mutant progenitors, whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer.”

    The authors were greatly intrigued by their findings and stated that their next steps include pursuing therapies, such as antibodies and herb-derived treatments that target the misguided progenitor cells, instead of only targeting the cancerous breast tissue they produce.

    “We think the way to treat breast cancer is to target the progenitor cells. We want to kill these cells that are feeding the tumor rather than just killing the tumor cells, which is less effective,” Dr. Ko concluded.