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The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

Title
The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer
Type
Article in International Scientific Journal
Year
2009
Authors
Fernandez, AF
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Rosales, C
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Lopez Nieva, P
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Grana, O
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Ballestar, E
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Ropero, S
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Espada, J
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Melo, SA
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Lujambio, A
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Fraga, MF
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Pino, I
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Javierre, B
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Carmona, FJ
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Acquadro, F
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Steenbergen, RDM
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Snijders, PJF
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Meijer, CJ
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Pineau, P
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Dejean, A
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Lloveras, B
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Capella, G
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Quer, J
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Buti, M
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Esteban, JL
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Allende, H
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Rodriguez Frias, F
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Castellsague, X
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Minarovits, J
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Ponce, J
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Capello, D
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Gaidano, G
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Cigudosa, JC
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Gomez Lopez, G
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Pisano, DG
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Valencia, A
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Piris, MA
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Bosch, FX
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Cahir McFarland, E
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Kieff, E
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Esteller, M
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Journal
Title: Genome ResearchImported from Authenticus Search for Journal Publications
Vol. 19
Pages: 438-451
ISSN: 1088-9051
Indexing
Other information
Authenticus ID: P-009-EQM
Abstract (EN): 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 I 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. © 2009 by Cold Spring Harbor Laboratory Press.
Language: English
Type (Professor's evaluation): Scientific
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