Genetics and epigenetics coregulate the cancer initiation and progression. Epigenetic mechanisms include DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs. Aberrant epigenetic modifications play a fundamental role in the formation of gastrointestinal cancers. Advances in epigenetics offer a better understanding of the carcinogenesis and provide new insights into the discovery of biomarkers for diagnosis, and prognosis prediction of human cancers. This review aims to overview the epigenetic aberrance and the clinical applications as biomarkers in gastrointestinal cancers mainly gastric cancer and colorectal cancer. 1. Introduction Cancer is one of the major disorders threatening our life. Gastrointestinal cancers mainly, including gastric cancer (GC) and colorectal cancer (CRC), account for a large proportion of human malignancies. They are both aggressive and the common cause of cancer-related deaths with a high disease-specific mortality rate around the world. There have been a great number of studies on the pathogenesis of gastrointestinal cancers. With a long history of chronic inflammation, GC and CRC result from the accumulation of both genetic and epigenetic changes that cause the transformation of normal cells into cancer cells. The classic genetic alterations are the mutations in key tumor suppressor genes or oncogenes, leading to defects of protein functions or deregulation of gene expression. In contrast, epigenetic events could affect gene expression without any changes in DNA sequence. 2. Overview of the Epigenetics The term epigenetics was coined in 1942 by C. H. Waddington when he was studying the causality between the genotype and the phenotype [1]. Now epigenetics refers to heritable modifications of the genome without any changes in primary DNA sequences [2]. In 1982, Feinberg and Vogelstein first discovered aberrant epigenetic alterations in human colorectal cancer [3]. Epigenetics which focuses on the process transforming genotype into phenotype is corresponding to genetics that refers to the heredity of genotype. Epigenetic alterations, like gene mutations, contribute to the pathogenesis and molecular heterogeneity of cancers. Epigenetics is different from the traditional genetics, mainly in the reversibility and position effect. The epigenetic modifications currently believed to play a role in cancers include DNA methylation, specific histone modifications, chromatin remodeling, and noncoding RNAs. 2.1. DNA Methylation The best-characterized epigenetic modification is methylation, a covalent addition of
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