來自西班牙國立癌癥研究中心等處的科研工作者在冷泉港出版社的Genome Research上發(fā)表文章,，解析病毒的表觀遺傳學(xué)變異對癌癥發(fā)生的關(guān)系,，為病毒致癌理論增添了新的內(nèi)容。
目前,，科學(xué)家們發(fā)現(xiàn)有15%的癌癥與病毒感染有直接的關(guān)聯(lián),，比如說,，子宮癌就與HPV有直接的關(guān)系,。
在這篇研究性文章中，科學(xué)家們進一步發(fā)現(xiàn)癌癥的發(fā)生與病毒DNA的甲基化有某些密切的關(guān)聯(lián),。DNA甲基化可能導(dǎo)致基因沉默,，而某些基因的沉默又與癌癥的發(fā)生有關(guān)聯(lián)。
Manel Esteller帶領(lǐng)研究小組繪制了三種致癌病毒的甲基化圖譜,，分別是HPV（人乳頭狀瘤病毒）,，HBV（乙肝病毒）和EBV。
每種病毒又分別在三種階段來繪制甲基化圖譜,，一種是病毒侵入細胞還不致病的早期,，一種是病毒侵入細胞引發(fā)早期癌癥癥狀的時期，一種是病毒侵入細胞已經(jīng)引發(fā)惡性癌癥的晚期,。研究者發(fā)現(xiàn)，癌癥癥狀越嚴(yán)重病毒的甲基化程度越深,。
對于這一結(jié)果,，研究人員Esteller推測，病毒面對宿主的免疫攻擊后衍生出新的逃避免疫攻擊的機制,，病毒通過甲基化沉默掉部分基因,，減少蛋白的表達量，越少蛋白表達就越少刺激宿主的免疫系統(tǒng),，病毒就以此來逃避免疫攻擊,。
研究人員稱，下一步將研究其他病毒的甲基化機制,，比如說HIV的甲基化與免疫逃避的關(guān)聯(lián),。（生物谷Bioon.com）
生物谷推薦原始出處：
Genome Res. 2009.Published in Advance February 10, 2009, doi:10.1101/gr.083550.108
The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer
Agustin F. Fernandez1,2, Cecilia Rosales1, Pilar Lopez-Nieva1, Osvaldo Gra?a3, Esteban Ballestar1, Santiago Ropero1, Jesus Espada1, Sonia A. Melo1, Amaia Lujambio1, Mario F. Fraga1, Irene Pino1, Biola Javierre1, Francisco J. Carmona1,2, Francesco Acquadro4, Renske D.M. Steenbergen5, Peter J.F. Snijders5, Chris J. Meijer5, Pascal Pineau6, Anne Dejean6, Belen Lloveras7, Gabriel Capella7, Josep Quer8, Maria Buti8, Juan-Ignacio Esteban8, Helena Allende9, Francisco Rodriguez-Frias10, Xavier Castellsague11, Janos Minarovits12, Jordi Ponce13, Daniela Capello14, Gianluca Gaidano14, Juan Cruz Cigudosa4, Gonzalo Gomez-Lopez3,15, David G. Pisano3, Alfonso Valencia3, Miguel Angel Piris16, Francesc X. Bosch11, Ellen Cahir-McFarland17, Elliott Kieff17,18 and Manel Esteller1,2,19,20
1Cancer Epigenetics Group, Spanish National Cancer Research Centre (CNIO), Madrid E-28029, Spain;
2Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research-Catalan Institute of Oncology (IDIBELL-ICO), Barcelona, Catalonia 08907, Spain;
3Bioinformatics Unit and Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid E-28029, Spain;
4Molecular Cytogenetics Group and CIBERER, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid E-28029, Spain;
5Department of Pathology, Unit of Molecular Pathology, Vrije Universiteit Medical Center, Amsterdam 1007 MB, The Netherlands;
6Nuclear Organization and Oncogenesis Unit, INSERM U579, Pasteur Institute, Paris 75724, France;
7Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Catalonia 08907, Spain;
8Liver Unit, Department of Medicine, Hospital Vall Hebron, and Universitat Autonoma Barcelona and CIBEREHD, Barcelona 08035, Spain;
9Pathology Department, Hospital Vall Hebron, Barcelona 08035, Spain;
10Departament Bioquimica, Hospital Vall Hebron and CIBEREHD, Barcelona 08035, Spain;
11Service of Epidemiology and Cancer Register, Catalan Institute of Oncology (ICO), Barcelona, Catalonia 08907, Spain;
12Microbiological Reseach Group, National Center for Epidemiology, Budapest 1529, Hungary;
13Service of Gynecology, Hospital Universitari de Bellvitge, L'Hospitalet, Catalonia 08907, Spain;
14Division of Hematology, Department of Clinical and Experimental Medicine and Department of Oncology, Amedeo Avogadro University of Eastern Piedmont, Vercelli, Alessandria, Novara 13100, Italy;
15Biomedical Foundation Complexo Hospitalario, Universitario de Vigo (CHUVI), Vigo 36211, Spain;
16Lymphoma Group, Molecular Pathology Programme, Spanish National Cancer Research Centre, Madrid E-28029, Spain;
17Departments of Medicine, Microbiology, and Molecular Genetics, Harvard University, Boston, Massachusetts 02115, USA;
18Infectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;
19Institucio Catalana de Recerca i Estudis Avan?ats (ICREA), Barcelona 08010, Spain
Abstract
The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses.
