Hypermethylation of the TFAP2E gene was correlated with nonresponsiveness of colorectal cancer to a commonly used chemotherapeutic agent.
In a study involving more than 200 patients in four independent cohorts, Prof. Ebert at the University of Heidelberg (Germany) and his team demonstrated that hypermethylation of the TFAP2E gene was correlated with nonresponsiveness of colorectal cancer to the commonly used chemotherapeutic agent 5-fluorouracil (5-FU). The study was reported in the January 2012 edition of the New England Journal of Medicine.
Using a combination of data from cancer cell lines and patient samples, the authors demonstrated that this effect was potentially mediated through up-regulation of the DKK4 gene, previously implicated in 5-FU resistance. Resistance to treatment was observed with 5-FU based chemotherapy or 5-FU chemotherapy combined with radiation, indicating that TFAP2E methylation may be a valuable biomarker for response prediction in either setting.
The study demonstrates the growing role that biomarkers can play in the management of cancer and other diseases. Prof. Ebert commented: “In practical terms, we believe this study demonstrates the potential that novel DNA methylation biomarkers may have in improving the selection of therapies for this deadly disease. A prospective validation of the marker is, however, still required.”
Epigenomics AG (Berlin, Germany and Seattle, WA, USA) scientists believe that the study demonstrates the potential of TFAP2E and other biomarkers identified in Epigenomics’ DNA methylation discovery pipeline in supporting clinical decision making.
Epigenomics’ lead product, Epi proColon, is a blood-based test for the early detection of colorectal cancer, which is currently marketed in Europe and is in development for the United States.
University of Heidelberg