Plasma methylated septin 9: a colorectal cancer screening marker

Colorectal cancer (CRC) is a slow-developing cancer (10-15 years) with one of the highest frequencies in the world's population. Many countries have implemented various CRC screening programs, but have not achieved the desired compliance. Colonoscopy - considered the gold standard for CRC screening - has its limitations as well as the other techniques used, such as irrigoscopy, sigmoidoscopy, fecal blood and hemoglobin tests. The biomarker septin 9 has been found to be hypermethylated in nearly 100% of tissue neoplasia specimens and detected in circulating DNA fractions of CRC patients. A commercially available assay for septin 9 has been developed with moderate sensitivity (∼70%) and specificity (∼90%) and a second generation assay, Epi proColon 2.0 (Epigenomics AG), shows increased sensitivity (∼92%). The performance of the assay proved to be independent of tumor site and reaches a high sensitivity of 77%, even in early cancer stages (I and II). Furthermore, septin 9 was recently used in follow-up studies for detection of early recurrence of CRC. This article evaluates the opportunities, known limitations and future perspectives of the recently introduced Epi proColon(®) 2.0 test, which is based on the detection of aberrantly methylated DNA of the v2 region of the septin 9 gene in plasma.