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00925njm 22002777a 4500 dc Fernández, Agustín F. author Rosales, Cecilia author López Nieva, Pilar author Graña Castro, Osvaldo author Ballestar Tarín, Esteban author Ropero, Santiago author Espada, Jesús author Melo, Sónia Rita Cardoso, 1978- author Lujambio, Amaia author Fraga, Mario F. author Pino, Irene author Javierre, Biola M. author Carmona Herrera, Francisco author Acquadro, Francesco author Steenbergen, Renske D.M. author Snijders, Peter J. F. author Meijer, Chris J. L. M. author Pineau, Pascal author Dejean, Anne author Lloveras Rubio, Betlem author Capellá, G. (Gabriel) author Quer, Josep author Buti, Maria author Esteban, Juan I. author Allende, Helena author Rodríguez-Frías, Francisco author Castellsagué, Xavier author Minarovits, Janos author Ponce i Sebastià, Jordi author Capello, Daniela author Gaidano, Gianluca author Cigudosa, Juan Cruz author Gómez López, Gonzalo author Pisano, David G. author Valencia, Alfonso author Piris, Miguel A. author Bosch José, Francesc Xavier, 1947- author Cahir-McFarland, Ellen author Kieff, Elliott author Esteller, Manel author 2020-11-18T13:22:58Z 2020-11-18T13:22:58Z 2009-03-01 2020-11-18T13:22:58Z 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. ADN Metilació Fisiologia Virus Genètica Genomes Càncer DNA Methylation Physiology Viruses Genetics Genomes Cancer The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer