TY - JOUR
T1 - DNA methylation in cancer
T2 - A gene silencing mechanism and the clinical potential of its biomarkers
AU - Fukushige, Shinichi
AU - Horii, Akira
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - Initiation and progression of human caner not only depends on genetic alterations but also on epigenetic changes such as DNA methylation and histone modifications. Aberrant DNA hypermethylation in the promoter regions of genes is the most well-defined epigenetic change in tumors and is associated with inappropriate gene silencing. This feature can be utilized to search for tumor-specific DNA methylation biomarkers and to examine candidate DNA biomarkers for clinical use. DNA methylation biomarker is defined as a molecular target that undergoes DNA methylation changes in carcinogenesis. Such a biomarker is useful for early detection of cancer, predicting and/or monitoring the therapeutic response, and detection of recurrent cancer. In this review, we describe the mechanism that establishes and maintains DNA methylation patterns as well as the mechanism of aberrant gene silencing in cancer, and then we introduce methods to isolate the DNA methylation biomarkers. We also summarize the current status of clinical implementation for some of the most widely studied and well-validated DNA methylation biomarkers, including tissue factor pathway inhibitor 2 (TFPI2), septin 9 (SEPT9), glutathione S-transferase pi 1 (GSTP1), and O6-methylguanine-DNA methyltransferase (MGMT), and assess the clinical potential of these biomarkers for risk assessment, early diagnosis, prognosis, treatment, and the prevention of cancer. Finally we describe the possible involvement of 5-hydroxymethylcytosine in cancer; this is a recently discovered 5-methylcytosine oxidation derivative and might have a diagnostic potential in certain cancers. Abnormal DNA methylations are leading candidates for the development of specific markers for cancer diagnosis and therapy.
AB - Initiation and progression of human caner not only depends on genetic alterations but also on epigenetic changes such as DNA methylation and histone modifications. Aberrant DNA hypermethylation in the promoter regions of genes is the most well-defined epigenetic change in tumors and is associated with inappropriate gene silencing. This feature can be utilized to search for tumor-specific DNA methylation biomarkers and to examine candidate DNA biomarkers for clinical use. DNA methylation biomarker is defined as a molecular target that undergoes DNA methylation changes in carcinogenesis. Such a biomarker is useful for early detection of cancer, predicting and/or monitoring the therapeutic response, and detection of recurrent cancer. In this review, we describe the mechanism that establishes and maintains DNA methylation patterns as well as the mechanism of aberrant gene silencing in cancer, and then we introduce methods to isolate the DNA methylation biomarkers. We also summarize the current status of clinical implementation for some of the most widely studied and well-validated DNA methylation biomarkers, including tissue factor pathway inhibitor 2 (TFPI2), septin 9 (SEPT9), glutathione S-transferase pi 1 (GSTP1), and O6-methylguanine-DNA methyltransferase (MGMT), and assess the clinical potential of these biomarkers for risk assessment, early diagnosis, prognosis, treatment, and the prevention of cancer. Finally we describe the possible involvement of 5-hydroxymethylcytosine in cancer; this is a recently discovered 5-methylcytosine oxidation derivative and might have a diagnostic potential in certain cancers. Abnormal DNA methylations are leading candidates for the development of specific markers for cancer diagnosis and therapy.
KW - Biomarker
KW - Cancer
KW - CpG island
KW - DNA methylation
KW - Gene silencing
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U2 - 10.1620/tjem.229.173
DO - 10.1620/tjem.229.173
M3 - Review article
C2 - 23419314
AN - SCOPUS:84874198889
VL - 229
SP - 173
EP - 185
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 3
ER -