Li Lili, Ma Brigette B Y, Chan Anthony T C, Chan Francis K L, Murray Paul, Tao Qian
Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Institute of Digestive Disease and State Key Laboratory of Digestive Diseases, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Pathogens. 2018 Jul 18;7(3):63. doi: 10.3390/pathogens7030063.
Cancer genome studies of Epstein-Barr virus (EBV)-associated tumors, including lymphoepithelioma-like carcinomas (LELC) of nasopharyngeal (NPC), gastric (EBVaGC) and lung tissues, and natural killer (NK)/T-cell lymphoma (NKTCL), reveal a unique feature of genomic alterations with fewer gene mutations detected than other common cancers. It is known now that epigenetic alterations play a critical role in the pathogenesis of EBV-associated tumors. As an oncogenic virus, EBV establishes its latent and lytic infections in B-lymphoid and epithelial cells, utilizing hijacked cellular epigenetic machinery. EBV-encoded oncoproteins modulate cellular epigenetic machinery to reprogram viral and host epigenomes, especially in the early stage of infection, using host epigenetic regulators. The genome-wide epigenetic alterations further inactivate a series of tumor suppressor genes (TSG) and disrupt key cellular signaling pathways, contributing to EBV-associated cancer initiation and progression. Profiling of genome-wide CpG methylation changes (CpG methylome) have revealed a unique epigenotype of global high-grade methylation of TSGs in EBV-associated tumors. Here, we have summarized recent advances of epigenetic alterations in EBV-associated tumors (LELCs and NKTCL), highlighting the importance of epigenetic etiology in EBV-associated tumorigenesis. Epigenetic study of these EBV-associated tumors will discover valuable biomarkers for their early detection and prognosis prediction, and also develop effective epigenetic therapeutics for these cancers.
对与爱泼斯坦-巴尔病毒（EBV）相关肿瘤的癌症基因组研究，包括鼻咽癌（NPC）、胃癌（EBVaGC）和肺组织的淋巴上皮瘤样癌（LELC）以及自然杀伤（NK）/T细胞淋巴瘤（NKTCL），揭示了基因组改变的一个独特特征，即与其他常见癌症相比，检测到的基因突变较少。现在已知表观遗传改变在EBV相关肿瘤的发病机制中起关键作用。作为一种致癌病毒，EBV利用劫持的细胞表观遗传机制在B淋巴细胞和上皮细胞中建立潜伏性和裂解性感染。EBV编码的癌蛋白利用宿主表观遗传调节因子调节细胞表观遗传机制，以重新编程病毒和宿主表观基因组，尤其是在感染早期。全基因组表观遗传改变进一步使一系列肿瘤抑制基因（TSG）失活，并破坏关键的细胞信号通路，导致EBV相关癌症的发生和发展。全基因组CpG甲基化变化（CpG甲基化组）分析揭示了EBV相关肿瘤中TSG全球高级别甲基化的独特表观基因型。在这里，我们总结了EBV相关肿瘤（LELC和NKTCL）表观遗传改变的最新进展，强调了表观遗传病因在EBV相关肿瘤发生中的重要性。对这些EBV相关肿瘤的表观遗传学研究将发现用于早期检测和预后预测的有价值生物标志物，并为这些癌症开发有效的表观遗传治疗方法。
