EBV相關性胃癌罕見p53基因突變的可能機制與意義
發(fā)布時間：2018-10-08 08:53
【摘要】：2014年癌癥基因組圖譜(The Cancer Genome Atlas,TCGA)首次將胃癌從分子水平分為四型,其中EB病毒(Epstein-Barr virus,EBV)感染型即EBV相關性胃癌(EBV-associated gastric cancer,EBVa GC)患者,可能是免疫治療的適宜群體。在包括胃癌在內(nèi)的大部分腫瘤中p53基因突變率最高,但在EBVa GC中p53基因突變率卻遠低于EBV陰性胃癌(EBV-negative gastric cancer,EBVn GC)�？赡軝C制為:EBV感染是EBVa GC形成的早期事件;野生型p53蛋白與病毒即刻早期蛋白BZLF1(Z)相互作用,維持EBV潛伏感染狀態(tài)和早期復制;病毒復制后期,野生型p53蛋白可在病毒產(chǎn)物的作用下通過泛素化等途徑被降解,以上或可表明p53基因野生型對EBVa GC形成的重要性。而EBV感染誘導炎癥反應,腫瘤組織中大量淋巴細胞浸潤,基因組高突變率及PD-L1擴增的特征使其可能成為免疫治療的適宜群體,也說明免疫微環(huán)境在腫瘤發(fā)生發(fā)展中的重要作用。而在EBVn GC中,多種因素導致p53基因突變率較高,使其失去正常的抑癌功能而導致腫瘤發(fā)生。本文就EBVa GC中罕見p53基因突變這一現(xiàn)象的可能機制進行綜述。
[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.
【作者單位】： 北京大學腫瘤醫(yī)院暨北京市腫瘤防治研究所惡性腫瘤發(fā)病機制及轉化研究教育部重點實驗室;
【分類號】：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.
【作者單位】： 北京大學腫瘤醫(yī)院暨北京市腫瘤防治研究所惡性腫瘤發(fā)病機制及轉化研究教育部重點實驗室;
【分類號】：R735.2
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