Study objectives and design. The principal aim of the PRESEPT Study is to prospectively evaluate the clinical performance of the SEPT9 DNA methylation biomarker for CRC screening. Toward this goal, the performance characteristics of the mSEPT9 biomarker for the detection of CRC in average to increased risk screening-guideline eligible individuals will be demonstrated. The performance characteristics of the mSept9 biomarker will furthermore be evaluated for the detection of polyps ≥ 1 cm and/or carcinoma in situ in the same study population. Methylation of the SEPT9 gene will be assessed in DNA isolated from plasma of individuals scheduled for screening colonoscopy and meeting the pre-defined inclusion/exclusion criteria. The study is designed as a prospective, open enrollment clinical investigation involving multiple clinical study sites in the United States and Germany. Subjects will be competitively enrolled until at least 50 colorectal adenocarcinoma cases (Stage I-IV), identified by colonoscopy and verified by histopathological examination, have been enrolled and included in the analysis. The collection of subjects’ plasma samples and clinical information will be conducted to support development of an in vitro diagnostic test as well as clinical laboratory test services for routine medical testing by Epigenomics, the sponsor of the PRESEPT Study, or its partners. It is also anticipated that data obtained in this study will be used to analyze the health economic impact of the mSept9 biomarker for CRC screening.
DNA methylation biomarkers. DNA methylation is a natural and tightly controlled biological process involved in the regulation of genes and the stability of the human genome. Cytosine, one of the four bases in DNA, can be modified by the covalent addition of a methyl group. DNA methylation in gene regulatory regions (i.e. gene promoters) helps control gene activity. Every cell type has its unique DNA methylation “fingerprint” that changes in various normal biological processes and in many diseases, in particular cancer.
Aberrantly methylated genes represent attractive cancer biomarkers candidates, since cancer-specific methylation changes occur early in tumorigenesis, appear stable, yield positive amplifiable signals, and can be assayed with high analytical sensitivity. Studies have shown that aberrantly methylated DNA markers can be detected in tissue (1, 2) and body fluids (3, 4) and are highly correlated with the presence of cancer. Through Epigenomics’ methylation marker discovery and verification process that includes multiple case control studies in hundred of patients and healthy individuals it was shown that some of these markers are indeed viable candidates for screening applications and warrant validation in the appropriate population.
The mSEPT9 biomarker. Epigenomics has discovered a DNA methylation biomarker found in blood, SEPT9, which is strongly associated with the presence of CRC. The SEPT9 gene encodes multiple polypeptides involved in in numerous cellular processes and is thought to play a role in the onset of cancer. Epigenomics has demonstrated in several clinical case control studies with over 3,250 samples from colorectal cancer patients, healthy controls, and patients with non-cancerous colon diseases that a methylated region of the SEPT9 gene shed by tumors into the blood stream can serve as a biomarker for the sensitive and specific detection of colorectal cancer.
mSEPT9 assay technology. The methylated SEPT9 DNA can be measured using technologies that distinguish between methylated cytosines and unmethylated cytosines. For the PRESEPT Study Epigenomics has optimized and clinically evaluated an assay system for the mSEPT9 biomarker that consists of a preanalytical process that yields high proportions of free-floating DNA from blood plasma and an analytical procedure based on Epigenomics proprietary real-time PCR technologies HeavyMethyl™ and MethyLight™ to detect methylated Sept9 DNA with high analytical sensitivity and specificity.
The information contained in this website does not constitute nor imply an offer to sell or transfer any product, and no product based on this technology is currently available for sale in the United States. The analytical and clinical performance characteristics of any product based on this technology which may be sold at some future time in the U.S. have not been established. For further important disclaimers please read here.
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