DNA methylation patterns as noninvasive biomarkers and targets of epigenetic therapies in colorectal cancer.
Aberrant DNA methylation is frequently detected in gastrointestinal tumors, and can therefore potentially be used to screen, diagnose, prognosticate, and predict colorectal cancers (CRCs). Although colonoscopic screening remains the gold standard for CRC screening, this procedure is invasive, expensive, and suffers from poor patient compliance. Methylated DNA is an attractive choice for a biomarker substrate because CRCs harbor hundreds of aberrantly methylated genes. Furthermore, abundance in extracellular environments and resistance to degradation and enrichment in serum, stool, and other noninvasive bodily fluids, allows quantitative measurements of methylated DNA biomarkers. This article describes the most important studies that investigated the efficacy of serum- or stool-derived methylated DNA as population-based screening biomarkers in CRC, details several mechanisms and factors that control DNA methylation, describes a better use of prevailing technologies that discover novel DNA methylation biomarkers, and illustrates the diversity of demethylating agents and their applicability toward clinical impact.
Center for Translational Genomics & Oncology, Baylor Scott & White Research Institute & Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Yutaka
Y
Hashimoto
Center for Translational Genomics & Oncology, Baylor Scott & White Research Institute & Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Timothy J
TJ
Zumwalt
Center for Translational Genomics & Oncology, Baylor Scott & White Research Institute & Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Ajay
A
Goel
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009857:Oncogenes; D017422:Sequence Analysis, DNA
D014408:Biomarkers, Tumor
DNA; biomarker; colorectal cancer; gene silencing; methylation; methylation-specific PCR; microarray; next-generation sequencing; prognosis; pyrosequencing