Abstract 3511: The translation of epigenetic colorectal cancer tissue based diagnostic biomarkers into both faecal and blood based diagnostic biomarkers.
Authors: Speight Graham , Workman Nicholas , Agashe Pooja , Stark Richard , Ball Stuart , Rogers Andrew , Colón Will , Anson John 
Published: August 2014

Colorectal cancer (CRC) is the 3rd most common cancer with &gt;1 million new cases diagnosed annually. It is estimated that there could be up to 20,000 fewer deaths from CRC over the next 20 years if 60% of those eligible undertook bowel screening.

In the UK, the current primary screening tool is the faecal occult blood test (FOBt). This test determines the presence of blood within a patients stool. It does not diagnose CRC directly, a positive test directs patients for further clinical evaluation. This potentially leads to invasive tests such as colonoscopy; however, the presence of blood in the faeces can be due to many factors and thus for every 10 people who undergo a colonoscopy, 7 individuals will have a ‘normal’ result. The poor positive predictive value of the FOBt test leads to unnecessary concern for the patient, has associated morbidity effects and has a huge cost implication for the healthcare system. Consequently, there is a need for a robust preventive strategy that can stratify patients into appropriate screening programmes for the early detection of CRC.

There is growing evidence for aberrant hypermethylation of CpG islands in patients who suffer from CRC. Molecular diagnostics companies are exploiting the detection of aberrant DNA hypermethylation of Vimentin in faeces and Septin-9 in blood to develop assays for CRC diagnosis. Both tests are currently undergoing clinical trials.

Here we present data from a panel of 12 genes with hypermethylated CpG sites that have been successfully validated in tissue samples. A subset (6 markers) of this panel has previously been shown to have extremely high sensitivity (94%) and specificity (98%) for carcinoma tissues, and importantly this performance is not eroded when tissue from pre-malignant adenoma samples are analysed (sensitivity 93%, specificity 98%). The areas under the Receiver Operating Characteristic curves were 0.984 for carcinomas and 0.968 for adenomas1.

We have developed and translated these 12 tissue markers, culminating in a multiplex method for the analysis of all 12 markers in both blood and faecal samples. Here we present the application of this multiplexed method for the detection of carcinomas in faecal/blood samples with high sensitivity and specificity. The resulting method is suitable for a population-based screening approach which provides enhanced sensitivities and specificities over the current FOBt test.

1. G. Lind et al., Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas, Molecular Cancer, vol. 10, 2011.

Citation Format: Graham Speight, Nicholas Workman, Pooja Agashe, Richard Stark, Stuart Ball, Andrew Rogers, Will Colón, John Anson. The translation of epigenetic colorectal cancer tissue based diagnostic biomarkers into both faecal and blood based diagnostic biomarkers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3511. doi:10.1158/1538-7445.AM2013-3511