| EBV相关性胃癌罕见p53基因突变的可能机制与意义 |
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| 引用本文： | 李北芳,高静. EBV相关性胃癌罕见p53基因突变的可能机制与意义[J]. 中国肿瘤临床, 2017, 44(11): 522-526. DOI: 10.3969/j.issn.1000-8179.2017.11.026 |
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| 作者姓名： | 李北芳 高静 |
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| 作者单位： | 北京大学肿瘤医院暨北京市肿瘤防治研究所恶性肿瘤发病机制及转化研究教育部重点实验室（北京市100142） |
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| 摘 要： | 2014年癌症基因组图谱（The Cancer Genome Atlas，TCGA）首次将胃癌从分子水平分为四型，其中EB病毒（Epstein-Barr virus，EBV）感染型即EBV相关性胃癌（EBV-associated gastric cancer，EBVaGC）患者，可能是免疫治疗的适宜群体。在包括胃癌在内的大部分肿瘤中p53基因突变率最高，但在EBVaGC中p53基因突变率却远低于EBV阴性胃癌（EBV-negative gastric cancer，EBVnGC）。可能机制为:EBV感染是EBVaGC形成的早期事件；野生型p53蛋白与病毒即刻早期蛋白BZLF1（Z）相互作用，维持EBV潜伏感染状态和早期复制；病毒复制后期，野生型p53蛋白可在病毒产物的作用下通过泛素化等途径被降解，以上或可表明p53基因野生型对EBVaGC形成的重要性。而EBV感染诱导炎症反应，肿瘤组织中大量淋巴细胞浸润，基因组高突变率及PD-L1扩增的特征使其可能成为免疫治疗的适宜群体，也说明免疫微环境在肿瘤发生发展中的重要作用。而在EBVnGC中，多种因素导致p53基因突变率较高，使其失去正常的抑癌功能而导致肿瘤发生。本文就EBVaGC中罕见p53基因突变这一现象的可能机制进行综述。
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| 关 键 词： | EBV相关性胃癌 p53基因突变 野生型p53蛋白 泛素化 免疫微环境 |
| 收稿时间： | 2017-01-09 |
Possible mechanism and significance of rare p53 mutation in Epstein-Barr virus-associated gastric cancer |
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| Beifang LI,Jing GAO. Possible mechanism and significance of rare p53 mutation in Epstein-Barr virus-associated gastric cancer[J]. Chinese Journal of Clinical Oncology, 2017, 44(11): 522-526. DOI: 10.3969/j.issn.1000-8179.2017.11.026 |
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| Authors: | Beifang LI Jing GAO |
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| Affiliation: | Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China |
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| Abstract: | In 2014, The Cancer Genome Atlas firstly classified gastric cancer into four types according to genotype. Epstein-Barr virus (EBV) positive gastric cancer or EBV-associated gastric cancer (EBVaGC) is attracting attention because it is a possibly suitable group for immunotherapy. Among the mutations observed in tumors, such as gastric cancer, p53 mutations are the most frequent. In particular, it occurs more frequently in EBVaGC than in EBV-negative gastric cancer (EBVnGC). Meanwhile, EBV infection is considered as an early event of tumorigenesis. The interactions between wild-type p53 proteins and BZLF1 (Z) proteins are essential in maintaining the latent state of EBV infection and promoting early replication. In the latter stages of replication, wild-type p53 proteins are degraded through the ubiquitination of some viral molecules. These findings may indicate the importance of wild-type p53 genes in EBVaGC formation. Inflammatory responses induced by EBV infection, tumor with a large number of lymphocyte infiltration, genome high mutation, and PD-L1 amplification make it possible to become the appropriate group of immunotherapy, which also illustrate that the important role of immune microenvironment during tumor progression. In EBVnGC, extremely high levels of p53 mutation were observed because of several associated factors, and the p53 protein encoded by the mutant p53 gene lost its antitumor function after tumorigenesis. In this review, the possible mechanisms of rare p53 mutation in EBVaGC are summarized. |
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| Keywords: | EBV-associated gastric cancer (EBVaGC) p53 gene mutation wild-type p53 protein ubiquitination immune microenviron-ment |
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