CpG methylation as epigenetic biomarkers for nasopharyngeal carcinoma diagnostics
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摘要CpG methylation at gene promoters or regulatory regions, as one of the well-studied epigenetic modifications, plays essential roles in normal physiology and the pathogenesis of nasopharyngeal carcinoma (NPC). Strongly associated with Epstein-Barr virus (EBV) infection, NPC manifests a unique epigenetic phenotype with high-grade genome-wide CpG methylation at CpG islands. Meanwhile, EBV acts as a strong epigenetic driver for NPC tumorigenesis. Through hijacking the cell epigenetic machinery (DNMTs, TETs, HDACs, etc.), EBV modulates the CpG methylation and histone modification profiles of both viral and cellular genes (especially tumor suppressor genes—TSG) to regulate their expression, even at the very early stage of NPC pathogenesis. It is believed that the high CpG methylation pressure and epigenetic dysregulation of gene expression induced by EBV infection create an ideal epigenetic environment in pre-malignant nasopharyngeal (NP) epithelial cells for further malignant transformation with subsequent genetic mutations, eventually potentiates NPC initiation and promotes its progression, together with genetic alterations. Clinically, tumor-specific methylation of TSG promoters can be used as epigenetic biomarkers. In this review, we summarized the recent development of TSG CpG methylation-based biomarkers for NPC diagnostics. We further discussed the advantages of DNA methylation biomarkers, the detection methods and sample sources (tissue biopsy, NP brushing, plasma). We believe that CpG methylation-based biomarkers using cell-free circulating DNA and NP brushing samples should have a great perspective for NPC diagnostics in future.CpG methylation at gene promoters or regulatory regions, as one of the well-studied epigenetic modifications, plays essential roles in normal physiology and the pathogenesis of nasopharyngeal carcinoma (NPC). Strongly associated with Epstein-Barr virus (EBV) infection, NPC manifests a unique epigenetic phenotype with high-grade genome-wide CpG methylation at CpG islands. Meanwhile, EBV acts as a strong epigenetic driver for NPC tumorigenesis. Through hijacking the cell epigenetic machinery (DNMTs, TETs, HDACs, etc.), EBV modulates the CpG methylation and histone modification profiles of both viral and cellular genes (especially tumor suppressor genes—TSG) to regulate their expression, even at the very early stage of NPC pathogenesis. It is believed that the high CpG methylation pressure and epigenetic dysregulation of gene expression induced by EBV infection create an ideal epigenetic environment in pre-malignant nasopharyngeal (NP) epithelial cells for further malignant transformation with subsequent genetic mutations, eventually potentiates NPC initiation and promotes its progression, together with genetic alterations. Clinically, tumor-specific methylation of TSG promoters can be used as epigenetic biomarkers. In this review, we summarized the recent development of TSG CpG methylation-based biomarkers for NPC diagnostics. We further discussed the advantages of DNA methylation biomarkers, the detection methods and sample sources (tissue biopsy, NP brushing, plasma). We believe that CpG methylation-based biomarkers using cell-free circulating DNA and NP brushing samples should have a great perspective for NPC diagnostics in future.
出版社接受日期24.12.2021
著者Lili Li, Jianlian Xie, Brigette Ma, Anthony TC Chan, Qian Tao
期刊名稱Annals of Nasopharynx Cancer
出版年份2022
出版社AME Publishing Company
出版地Hong Kong
電子國際標準期刊號2616-4191
語言美式英語