在肝癌的一种新病毒

StephenW

                    Public Release: 27-Aug-2015                    A new virus in liver cancer                                                

INSERM (Institut national de la santé et de la recherche médicale)

   

            
  
  

                                    More than a cause of a simple infection, viruses are often involved in the development of serious diseases. Such is the case with liver cancer, which often develops in an organ that has been weakened by hepatitis B or C virus. Researchers at Inserm, the Paris Public Hospitals (AP-HP), Paris Descartes University, Paris 13 University (USPC), and Paris Diderot University have just identified the role of a new virus, hitherto unsuspected, in the occurrence of a rare type of liver cancer.
This study, based on follow-up and observation of 193 patients, is published in the 24 August issue of Nature Genetics.
        With over 8,000 new individuals diagnosed annually, liver cancer mainly affects men, and is a major cause of death worldwide. Among the different types of liver cancer, hepatocellular carcinoma usually occurs in a liver that has already been damaged by illness. The liver may, for example, have been weakened by excessive alcohol consumption, obesity, or chronic viral infection by hepatitis B or C viruses, which causes irreversible liver lesions leading to cirrhosis.
        Cirrhosis patients generally undergo regular tests to detect cancer. However, in 5% of cases, liver cancer occurs in patients who had not reported cirrhosis, and the reason for developing the cancer remains to be identified.
        Jessica Zucman-Rossi and her staff at Inserm Unit 1162, "Functional Genomics of Solid Tumors," focused on these patients to determine the risk factors that had contributed to the development of their cancer.
        In the genome of tumour cells of 11 patients, the scientists observed the insertion of a viral DNA segment from adeno-associated virus type 2, known as AAV2. This virus has been considered non-pathogenic for humans until now. In order to confirm the virus's involvement in the cancer, the research team compared tumour tissues with normal tissues. They thus confirmed their hypothesis: the integration of viral DNA was found more often in tumour cells than in healthy cells in these 11 patients. Moreover, 8 of these patients did not have cirrhosis, and 6 of them presented no known risk factors for liver cancer.
        By studying these malignant cells in greater detail, they discovered that the virus, when inserting its DNA into the genome of the patient's cells, targets genes that are important in cell proliferation. Jessica Zucman-Rossi and her colleagues have shown that AAV2 leads to excessive expression of these genes which, according to the researchers, may favour tumour development.
By this work, the researchers have identified the involvement of AAV2 virus, previously thought to be harmless, in the occurrence of hepatocellular carcinoma, particularly in the rare cases of cancer that develop in the absence of cirrhosis and without an identified cause.
        These results also call for caution: "AAV2 is often used as a vector in gene therapy. Although the insertion of its DNA into tumour promoting genes is rare, and probably a chance event, precautions must be taken regarding the use of this virus," explain the authors.

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        This work was supported by the French National Cancer Institute (INCa) via ICGC and PAIR-CHC NoFLIC (with the participation of ARC Foundation) and the French National Cancer League. Tumour sequencing was performed by IntegraGen, in its laboratories located at Genopole, Evry.
        SOURCES
        Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas Jean-Charles Nault*1,2,3,4,5,15, Shalini Datta*1,2,3,4,15, Sandrine Imbeaud*1,2,3,4,15, Andrea
Franconi1,2,3,4, Maxime Mallet1,2,3,4, Gabrielle Couchy1,2,3,4, Eric Letouzé1,2,3,4, Camilla
Pilati1,2,3,4, Benjamin Verret1,4, Jean-Frédéric Blanc6,7, Charles Balabaud7, Julien
Calderaro1,2,3,4,8, Alexis Laurent9,10, Mélanie Letexier11, Paulette Bioulac-Sage7,12, Fabien
Calvo1,2,3,4,13, Jessica Zucman-Rossi1,2,3,4,14
        *Legal contribution
1 Inserm, UMR-1162, Functional Genomics of Solid Tumors, French National Cancer League-Designated Team, Paris, F-75010 France
2 Paris Descartes University, Labex Immuno-Oncology, Sorbonne Paris Cité, F-75010 Paris, France
3 Paris 13 University, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France.
4 Paris Diderot University, IUH, F-75010 Paris
5 AP-HP, Paris University Hospitals - Seine Saint-Denis, Site Jean Verdier, Specialist Oncology Unit, Hepatology Service, F-93143 Bondy, France
6 Bordeaux University Hospital, Department of Hepatology, Saint-André Hospital, Bordeaux, F-33076, France
7 Inserm, Joint Research Unit 1053; University of Bordeaux, Bordeaux, F-33076, France
8 Paris Public Hospitals (AP-HP), Department of Pathology, Henri Mondor University Hospital, F-94000 Créteil, France
9 Paris Public Hospitals (AP-HP), Department of Digestive and Hepatobiliary Surgery, Henri Mondor University Hospital, F-94000 Créteil, France
10 Inserm, U955, F-94000 Créteil, France
11 IntegraGen, Evry, F-91000, France
12 Bordeaux University Hospital, Pellegrin Hospital, Department of Pathology, Bordeaux, F-33076, France
13 Gustave Roussy Institute, Core Europe, Villejuif, F-94800, France
14 Paris Public Hospitals (AP-HP), George Pompidou European Hospital, F-75015 Paris, France
15 These authors contributed equally to this work.
Nature Genetics, 24 August 2015,
        INVESTIGATOR CONTACT
        Jessica Zucman-Rossi
University Professor and Hospital Practitioner (PU-PH), Paris Descartes University
Director of Unit 1162 "Functional Genomics of Solid Tumors" (Inserm/ Paris Descartes University / Paris 13 University / Paris Diderot University)
Oncology Service, George Pompidou European Hospital AP-HP
+ 33 (0)1 53 72 51 66
[email protected]
       

StephenW

公开发布：27月 - 2015年
在肝癌的一种新病毒

INSERM（国家研究所德拉桑特等德拉RECHERCHE MEDICALE）

以上简单的感染原因，病毒经常参与重大疾病的发展。这就是肝癌，这往往是在已经被削弱了乙型或丙型肝炎病毒器官的情况。研究人员在INSERM，巴黎公立医院（AP-HP），巴黎第五大学，巴黎第十三大学（USPC），和巴黎第七大学刚刚发现了一种新病毒，迄今没有料​​到的角色，在一个罕见的发生肝癌。

这项研究的基础上，随访和观察的193例患者，发表在自然遗传学的8月24日发行。

拥有逾8,000名新个人每年被诊断，肝癌的主要影响男性，并且是世界死亡的重要原因。在不同类型的肝癌，肝细胞癌通常发生在已被损坏的疾病肝脏。肝脏可以是，例如，已经削弱了过量饮酒，肥胖，或慢性病毒感染由乙型或丙型肝炎的病毒，这会导致不可逆的肝脏病变导致肝硬化。

肝硬化患者一般进行定期检查，以查出癌症。然而，在5％的病例，肝癌发生在谁没有报告肝硬化的患者，以及用于开发癌症的原因仍有待确定。

杰西卡Zucman - 罗西和她的工作人员INSERM单位1162，“实体瘤的功能基因组学”，集中在这些患者确定了其癌症的发展作出了贡献的危险因素。

在11名患者的肿瘤细胞的基因组中，科学家观察到腺相关病毒2型，被称为AAV2病毒DNA片段的插入。此病毒被认为是非致病对人类直到现在。为了证实该病毒的参与癌症，研究团队比较肿瘤组织与正常组织。因此，他们证实了他们的假设：病毒DNA的整合被发现更经常在肿瘤细胞中比在健康细胞中这11例患者。此外，这些患者8没有肝硬化，和其中6提出没有已知的危险因素的肝癌。

通过更详细地研究这些恶性细胞，他们发现该病毒，插入其DNA导入患者的细胞的基因组时，目标基因是细胞增殖重要的。杰西卡Zucman - 罗西和她的同事已经表明，AAV2导致这些基因，据研究人员介绍，可能有利于肿瘤发展的过度表达。

通过这项工作中，研究人员已经确定AAV2病毒的参与下，以前被认为是无害的，在肝癌的发生，特别是在癌症的罕见的情况下是开发在不存在肝硬化和未经识别的原因。

这些结果还呼吁谨慎：“AAV2经常被用来作为基因治疗的载体虽然它的DNA的插入肿瘤促进基因是罕见的，而且可能是一个随机事件，必须采取预防措施就使用这种病毒。”说明作者。

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这项工作是由法国国家癌症研究所（INCA）通过ICGC和成对CHC NoFLIC（与ARC基金的参与）和法国国家抗癌联盟的支持。肿瘤测序由IntegraGen进行，其实验室位于Genopole，埃夫里。

来源

经常AAV2相关的插入突变在人类肝细胞癌让查尔斯Nault * 1,2,3,4,5,15，Shalini达塔* 1,2,3,4,15，桑德琳Imbeaud * 1,2,3,4 15，安德烈
Franconi1,2,3,4，马克西姆Mallet1,2,3,4，加布里埃尔Couchy1,2,3,4，埃里克Letouzé1,2,3,4，卡米拉
Pilati1,2,3,4，本杰明Verret1,4，让 - 弗雷德里克Blanc6,7，查尔斯Balabaud7，朱利安
Calderaro1,2,3,4,8，亚历克西斯Laurent9,10，梅拉妮Letexier11，莫兰Bioulac-Sage7,12，法比安
Calvo1,2,3,4,13，杰西卡Zucman，Rossi1,2,3,4,14

*法律贡献
1 INSERM，UMR-1162，实体瘤的功能基因组学，法国国家抗癌联盟，专人专责，巴黎，F-75010法国
2巴黎第五大学，Labex免疫肿瘤，巴黎的索邦大学太阳城，F-75010巴黎，法国
3巴黎13大学，索邦大学巴黎太阳城，UFR SMBH，F-93000博比尼，法国。
4巴黎第七大学，IUH，F-75010巴黎
5 AP-HP，巴黎大学医院 - 塞纳圣但尼，网站让迭尔，专家肿瘤科，肝病服务，F-93143邦迪，法国
6波尔多大学附属医院，肝病，圣安德烈医院，波尔多，F-33076，法国系
7 INSERM，联合研究组1053;波尔多大学，波尔多，F-33076，法国
8巴黎公立医院（AP-HP），病理，亨利Mondor大学医院，F-94000克雷泰伊，法国系
9巴黎公立医院（AP-HP），消化系统及肝胆外科，亨利Mondor大学医院，F-94000克雷泰伊，法国系
10 INSERM，U955，F-94000克雷泰伊，法国
11 IntegraGen，埃夫里，F-91000，法国
12波尔多大学附属医院，佩列格林医院病理科，波尔多，F-33076，法国系
13古斯塔夫·鲁西研究所，欧洲核心国家，维勒瑞夫，F-94800，法国
14巴黎公立医院（AP-HP），乔治·蓬皮杜欧洲医院，F-75015巴黎，法国
15这些作者同等贡献这项工作。
自然遗传学，2015年24月，

调查员联系我们

杰西卡Zucman，罗西
大学教授和医院医生（PU-PH），巴黎第五大学
部总监1162“实体瘤的功能基因组学”（INSERM /巴黎第五大学/巴黎13大学/巴黎第七大学）
肿瘤科服务，蓬皮杜欧洲医院AP-HP
+ 33（0）1 53 72 51 66
[email protected]

默然10

AAV2 是这个病毒的名字吗？ 是说在调查11例没有肝硬化直接HCC 是这个AAV2有关系？

StephenW

回复 默然10 的帖子

AAV2 是这个病毒的名字吗？是.

调查11例HCC , 于 这个AAV2有关系. 8/11 没有肝硬, 6/11 没有已知肝癌的因素.

MP4

AAV2经常被用来作为基因治疗的载体虽然它的DNA的插入肿瘤促进基因是罕见的，而且可能是一个随机事件，必须采取预防措施就使用这种病毒

MP4

应该新药在用AAV，看来当初国家不批准有些道理