Abstract
Colorectal cancer (CRC) is a common malignancy and the fourth leading cause of cancer deaths worldwide. It results from the accumulation of multiple genetic and epigenetic changes leading to the transformation of colon epithelial cells into invasive adenocarcinomas. In CRC, epigenetic changes, in particular promoter CpG island methylation, occur more frequently than genetic mutations. Hypermethylation contributes to carcinogenesis by inducing transcriptional silencing or downregulation of tumour suppressor genes and currently, over 600 candidate hypermethylated genes have been identified. Over the past decade, a deeper understanding of epigenetics coupled with technological advances have hinted at the potential of translating benchtop research into biomarkers for clinical use. DNA methylation represents one of the largest bodies of literature in epigenetics, and hence has the highest potential for minimally invasive biomarker development. Most progress has been made in the development of diagnostic markers and there are currently two, one stool-based and one blood-based, biomarkers that are commercially available for diagnostics. Prognostic and predictive methylation markers are still at their infantile stages.
Highlights
Colorectal cancer (CRC) is the third most common cause of cancer in men and the second in women worldwide, with an estimated 1.36 million total number of new cases in 2012 [1]
We focus on hypermethylation, hypomethylation and a subset of CRCs called CpG Island Methylator Phenotype (CIMP)
This further supports the CIMP tumours observed in interval cancers, defined as CRCs that develop within five years of complete colonoscopy, which was found to be more prevalent (57%) in interval than in non-interval cancers (33%)
Summary
Colorectal cancer (CRC) is the third most common cause of cancer in men and the second in women worldwide, with an estimated 1.36 million total number of new cases in 2012 [1]. Building on the 1990 Vogelstein model, it is recognised that colorectal cancer is driven by the accumulation of genetic abnormalities, through mutations and genomic instabilities, as well as epigenetic alterations [5] In carcinogenesis, these changes often lead to gain of function in oncogenes or loss of function in tumour suppressor genes [6]. The identification of cell-free nucleic acid in various bodily fluids and stool increases the possibility of detecting methylated biomarkers noninvasively [3] Taken together, these biomarkers present a powerful approach to improve on the current diagnostic techniques and to optimise therapeutic decision-making, to achieve earlier diagnosis and lower the number of CRC morbidity and mortality. We discuss the translation of epigenetic research into the development of potential DNA methylation-based biomarkers as diagnostic, prognostic and predictive tools in the clinic, as well as explore the myriad of technologies that are frequently used to detect these methylation biomarkers
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