Stool DNA methylation assays in colorectal cancer screening

Abstract

Colorectal cancer (CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive non-invasive CRC screening test, there is the need for further research in several areas - establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.

Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples

“…Another CRC screening technique is stool-based analysis of abnormal DNA modifications, such as DNA mutation and methylation, as these alterations have an essential role in tumor formation. [9][10][11][12] Cologuard Ò (Exact Sciences Corporation, Madison, WI, United States) is a US FDA approved multitarget stool DNA test, which includes molecular assays for the detection of aberrantly methylated and mutated genes. As Imperiale et al showed in their recent work, the test has higher sensitivity for finding CRC in comparison to FIT; however, the detection of adenoma patients is less effective.…”

Significant association of EED promoter hypomethylation with colorectal cancer

“…Previous studies have revealed that DNA cytosine modifications serve an important role in cancer biology, and provide promising biomarkers for cancer diagnosis and prognosis evaluation (10,34). Several epigenetic biomarkers have been studied for the diagnosis of CRC, including SEPT9 (35), BMP3, NDRG4 (36) and hMLH1 (37). The ROC curves generated in the current study demonstrated that EED hypomethylation is a good biomarker for the diagnosis of CR.…”

DNA Methylation as a Noninvasive Epigenetic Biomarker for the Detection of Cancer

“…This is a result of the copious amounts of DNA shed from the tumour cells from the thoracic and oral regions into sputum and saliva. Stool can also be used to detect tumour-derived methylated DNA biomarkers for colorectal cancer [ 34 – 36 ] and pancreatic cancer [ 37 ]. A large proportion of the sample types evaluated to detect circulating cell-free biomarkers are blood based [ 38 , 39 ] in the detection of many cancers [ 40 , 41 ] as it contains a high volume of genetic material.…”