EBV相关性胃癌罕见p53基因突变的可能机制与意义
发布时间：2018-10-08 08:53
【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,EBVa GC)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EBVa GC中p53基因突变率却远低于EBV阴性胃癌(EBV-negative gastric cancer,EBVn GC)。可能机制为:EBV感染是EBVa GC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EBVa GC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EBVn GC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EBVa GC中罕见p53基因突变这一现象的可能机制进行综述。
[Abstract]:The 2014 cancer genome map (The Cancer Genome Atlas,TCGA) for the first time divides gastric cancer into four types from the molecular level, in which EB virus (Epstein-Barr virus,EBV) infected patients with EBV associated gastric cancer (EBV-associated gastric cancer,EBVa GC) may be a suitable population for immunotherapy. The mutation rate of p53 gene is the highest in most tumors, including gastric cancer, but the mutation rate of p53 gene in EBVa GC is much lower than that in EBV negative gastric cancer (EBV-negative gastric cancer,EBVn GC). The possible mechanism is that the infection of: EBV is the early event of EBVa GC formation; wild-type p53 protein interacts with the immediate early protein BZLF1 (Z) of the virus to maintain the latent infection state and early replication of EBV; The wild-type p53 protein can be degraded by ubiquitization under the action of virus products, which may indicate the importance of wild-type p53 gene in the formation of EBVa GC. However, EBV infection induces inflammatory reaction, a large number of lymphocytes infiltrate in tumor tissues, high genomic mutation rate and the characteristics of PD-L1 amplification, which may make it a suitable population for immunotherapy. It also shows that immune microenvironment plays an important role in the development of tumor. In EBVn GC, many factors lead to high mutation rate of p53 gene, which leads to the loss of normal tumor suppressor function and tumorigenesis. This article reviews the possible mechanism of the rare mutation of p53 gene in EBVa GC.
【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;
【分类号】：R735.2
[Abstract]:The 2014 cancer genome map (The Cancer Genome Atlas,TCGA) for the first time divides gastric cancer into four types from the molecular level, in which EB virus (Epstein-Barr virus,EBV) infected patients with EBV associated gastric cancer (EBV-associated gastric cancer,EBVa GC) may be a suitable population for immunotherapy. The mutation rate of p53 gene is the highest in most tumors, including gastric cancer, but the mutation rate of p53 gene in EBVa GC is much lower than that in EBV negative gastric cancer (EBV-negative gastric cancer,EBVn GC). The possible mechanism is that the infection of: EBV is the early event of EBVa GC formation; wild-type p53 protein interacts with the immediate early protein BZLF1 (Z) of the virus to maintain the latent infection state and early replication of EBV; The wild-type p53 protein can be degraded by ubiquitization under the action of virus products, which may indicate the importance of wild-type p53 gene in the formation of EBVa GC. However, EBV infection induces inflammatory reaction, a large number of lymphocytes infiltrate in tumor tissues, high genomic mutation rate and the characteristics of PD-L1 amplification, which may make it a suitable population for immunotherapy. It also shows that immune microenvironment plays an important role in the development of tumor. In EBVn GC, many factors lead to high mutation rate of p53 gene, which leads to the loss of normal tumor suppressor function and tumorigenesis. This article reviews the possible mechanism of the rare mutation of p53 gene in EBVa GC.
【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;
【分类号】：R735.2
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