DNA methylation biomarkers as diagnostic and prognostic tools in colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most common type of cancer and is responsible for 9 % of cancer deaths in both men and women in the USA for 2013. It is a heterogenous disease, and its three classification types are microsatellite instability, chromosomal instability, and CpG island methylator phenotype. Biomarkers are molecules, which can be used as indicators of cancer. They have the potential to achieve great sensitivities and specificities in diagnosis and prognosis of CRC. DNA methylation biomarkers are epigenetic markers, more specifically genes that become silenced after aberrant methylation of their promoter in CRC. Some methylation biomarkers like SEPT9 (ColoVantage®) and vimentin (ColoSure(TM)) are already commercially available. Other blood and fecal-based biomarkers are currently under investigation and clinical studies so that they can be used in the near future. Biomarker panels are also currently being studied since they show great potential in diagnosis as they can combine robust biomarkers to achieve even greater sensitivities than single markers. Finally, methylation-sensitive microRNAs (miRNAs) are very promising markers, and their investigation as biomarkers, is only at primitive stage.

A novel DNA methylation panel accurately detects colorectal cancer independently of molecular pathway

“…However, SEPT9 promoter methylation performance in CRC detection has been recently questioned [22]. As for Vimentin promoter methylation, this test is used in combination with colonoscopy, but sensitivity is rather variable, ranging from 38 to 88% [28,29]. Thus, alternative screening test is demanded to increase population adherence and perfect detection accuracy.…”

936 Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer

“…Indeed, similar observations with respect to differences in the frequencies of methylation between high-and low-grade bladder tumors were first suggested by Ibragimova et al 47 Similar subtype and/or grade-associated differences have been reported in other tumor types including, pituitary, breast, and colon cancer subtypes. 37,48,49 In our analysis of NMIBC it remains unclear whether the increase in frequency and/or mean levels of methylation in the more aggressive tumors represents a more rapid accumulation of epigenetic changes during tumor progression, or reflects distinct epigenetic pathways of tumor development and outgrowth. 50,51 Our findings may therefore reflect either of the described scenarios in the more aggressive (high-grade) tumors and suggests that these tumors are either consequent to progression from low-intermediategrade tumors, or are the progeny of aberrations in distinct epigenetic pathways within these NMIBC subtypes.…”

Epi proColon®: Use of a Non-Invasive SEPT9 Gene Methylation Blood Test for Colorectal Cancer Screening: A National Laboratory Experience

“…Alterations to normal DNA methylation patterns during early carcinogenesis make these events valuable markers for the early detection of cancer [10,11]. As a highly recognized alteration associated with a variety of human cancers, DNA hypermethylation typically occurs at CpG islands located in the promotor region of a gene, inactivating tumor suppressor genes and silencing transcription [10,12,13].…”

“…A complex set of epigenetic mechanisms regulate gene expression in both normal and cancerous tissue [13]. Aberrant DNA methylation, the most studied of these mechanisms in CRC, contributes to its heterogeneity and can be identified by unique methylated gene signatures [18].…”