Reza Zarnegar and colleagues, at the University of Pittsburgh, Pittsburgh, have determined that genetic variation in a piece of DNA that regulates activity of the HGF gene might be a useful marker to identify individuals with an increased risk of developing breast cancer.
The research appears online, Feb. 2nd, 2009, in the Journal of Clinical Investigation.
The HGF gene is not active in normal breast epithelial cells. However, its activity is not repressed in tumor samples from many patients with breast cancer. In the study, the authors identified a DNA region that controls the activity of the HGF gene and named it DATE (deoxyadenosine tract element).
Functional studies determined that shortening the DATE region led to activation of the HGF gene in cell lines. Further analysis indicated that a substantial proportion of patients with breast cancer have shortened DATE regions, and that these patients were markedly younger than patients with a DATE region of normal length.
Given these data, the authors suggest that future studies should investigate whether shortened DATE regions are also associated with other cancers that overexpress HGF, such as some forms of colon, stomach, pancreatic, endometrial, and cervical cancer.
- Jihong Ma, Marie C. DeFrances, Chunbin Zou, Carla Johnson, Robert Ferrell, Reza Zarnegar. Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer. J. Clin. Invest., 2009; DOI: 10.1172/JCI36640
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