In humans, DNA methylation typically occurs at the cytosine base of DNA, within CpG dinucleotides. What is interesting is the existence of CpG-rich regions – “CpG islands” – that are associated with the 5’-end regulatory regions of almost all housekeeping genes as well as with half of tissue-specific genes. When these promoter CpG islands are methylated, the associated genes tend to be transcriptionally inactive.

Indeed the correct expression of many tissue-specific, germline-specific, imprinted, and X-chromosome inactivated (in females) genes, as well as that of repetitive genomic sequences, relies largely on DNA methylation.

This means that every cell type has a unique DNA methylation fingerprint that changes during normal biological processes and many diseases, in particular
cancer¹.

The biomarker ^mSEPT9

The Epi proColon Early Detection Assay is based on detecting aberrantly methylated DNA of the v2 region of the Septin9 gene (SEPT9) in blood plasma.  Cytosine residues in the v2 region of the Septin9 gene are specifically methylated in colorectal cancer tissue but not in normal colon mucosa².

This tumor-specific methylation pattern can be used to amplify specifically cell-free DNA shed into the blood stream by tumor cells. Detection of colorectal cancer-derived DNA in blood plasma using the Septin9 methylation biomarker (^mSEPT9) has been demonstrated in multiple case control studies with CRC patients and colonoscopy-verified negative controls to be a reliable indicator of the presence of colorectal cancer^3-5.

What do we know about Septin9? 

The gene SEPT9 codes for the Septin9 protein, a member of a conserved family of GTP-binding proteins. Septins are multifunctional proteins, involved in vesicle trafficking, apoptosis, cytoskeletal remodelling, infection, neurodegeneration, neoplasia (i. e. cancer), among other important cellular processes. 

↓ References  

1. Esteller, M. Relevance of DNA methylation in the management of cancer. The Lancet Oncology 4, 351–358 (2003)
2. Model, F., et al. Identification and validation of colorectal neoplasia-specific methylation markers for accurate classification of disease. Mol Cancer Res 5, 153–163 (2007)
3. Lofton-Day, C. et al. DNA methylation biomarkers for blood-based colorectal cancer screening. Clinical Chemistry 54:2, 414–423 (2008)
4. Gruetzmann, R. et al. Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay. PLoS ONE, Volume 3, Issue 11, e3759 (2008)
5. De Vos, T. et al. Circulating methylated SEPT9 DNA in Plasma is a Biomarker for Colorectal Cancer, Clinical Chemistry, 55:7, 1337–1346 (2009)