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Epigenetic Changes in Virus-Associated Neoplasms

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Patho-Epigenetics of Disease

Abstract

The viruses associated with malignant tumors in humans include DNA viruses (Epstein–Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), human papillomavirus, Merkel cell polyomavirus) and a retrovirus replicating through a DNA intermediate (human T-lymphotropic virus, HTLV). Although Merkel cell polyomavirus remains yet to be studied, the expression of human tumor virus genomes is certainly affected by the cellular epigenetic machinery. A remarkable exception is hepatitis C virus (HCV), which causes a persistent infection: as far as we know, the RNA genome of HCV is exempt from the epigenetic control of the host cell.

All of the human tumor viruses code for oncoproteins capable to modulate the epigenome of the host cell. The latent membrane protein 1 (LMP1) of EBV upregulates all three cellular DNA methyltransferases (DNMTs) as well as the PcG group protein Bmi-1, resulting in silencing of cellular promoters. LMP2, also encoded by EBV, may induce DNMT1, similarly to LMP1. LANA, a latency-associated nuclear antigen of KSHV recruits DNMTs and histone deacetylases to the chromatin of selected cellular promoters. The HTLV-encoded Tax displaces transcription factors from the promoter of Shp1, a gene coding for the Src homology containing protein tyrosine phosphatase, followed by promoter hypermethylation. The viral oncoprotein HB-X (also called pX), a pleiotropic regulator expressed in hepatocarcinoma cells carrying HBV genomes, inhibits the expression of selected tumor suppressor genes by upregulating DNMT1 and DNMT3A. The HCV core protein is capable to activate DNMT1 and DNMT3B, to silence a distinct set of promoters in HCV-associated liver cancer. Gene suppression is achieved by the E6 oncoprotein in HPV-transformed cells by blocking the activities of coactivator protein arginine and protein lysine methyltransferases. The E7 oncoprotein of the highly oncogenic human papillomavirus, HPV-16, may induce hypermethylation of selected cellular promoters both directly, by binding to DNMT1 and stimulating its activity, and indirectly, by releasing the so-called “activating” E2F transcription factors that are complexed with members of the retinoblastoma pocket protein family. E2F activates DNMT1 transcription. A similar, indirect mechanism may operate in Merkel cell carcinomas expressing the tumor antigen (TAg) of Merkel cell polyomavirus, resulting in silencing of ATOH1, a master regulator gene.

Activating DNA and chromatin modifications regularly also occur in virus-associated neoplasms. The nuclear antigen EBNA1 of EBV may induce local, whereas HB-X of HBV may elicit global DNA hypomethylation. HB-X acts by downregulating DNMT3B involved in the methylation of satellite 2 repeat sequences. The EBV nuclear antigen EBNA2, a transactivator protein, interacts with histone acetyltransferases to establish an activating chromatin conformation at cellular and viral promoters. The coactivator EBNA-LP (EBNA5) promotes this process by the displacement of the histone deacetylase HDAC4 from EBNA2-activated promoters. Whereas LMP1 silences certain promoters in EBV-infected cells, in parallel it activates others. LMP1 induces KDM6B, a histone H3K27me3 demethylase which removes the trimethyl mark from lysine 27 of histone H3 and thereby dissociates PRC1 (polycomb repressive complexes) from their binding sites, resulting in target gene activation. In KSHV-infected cells, LANA also can act both as a silencer and as an activator of promoter activity in a context-dependent manner. MeCP2, a methylcytosine-binding protein, may facilitate both the repressor and the transactivating function of LANA, depending on the promoter analyzed. In addition, LANA induces changes in the positioning of chromosomal domains in interphase nuclei. E7 also has a dual function, involved not only in gene silencing but also in gene activation. In human keratinocytes, HPV-16 E7 increased histone H3 acetylation at the E2F1 and CDC25A promoters. In addition, similarly to LMP1, E7 modulates histone methylation patterns as well: it induces the lysine demethylases KDM6A and KDM6B that target histone H3K27me3 and disrupt polycomb repressor complexes. Elucidation of the complex virus-induced pathoepigenetic alterations may pinpoint new targets for the therapy of virus-associated neoplasms.

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Abbreviations

5-caC:

5-Carboxylcytosine

5-hmC:

5-Hydroxymethylcytosine

5-mC:

5-Methylcytosine

AIDS-BL:

AIDS-related-BL

APC:

Adenomatous polyposis coli

BART:

BamHI A rightward transcripts

BCBL:

Body cavity-based lymphoma

BL:

Burkitt’s lymphoma

CBF1:

C promoter-binding factor 1

CGI:

CpG island

cHL:

Classical Hodgkin’s lymphoma

CIMP:

CpG island methylator phenotype

CIN:

Cervical intraepithelial neoplasm

CIN:

Chromosomal instability

Cp:

C promoter

CpG:

Cytosine-phosphate-guanine dinucleotide

CRBP:

Cellular retinol-binding protein

CTCF:

CCCTC-binding factor

DLBCL:

Diffuse large B-cell lymphoma

DNMT:

DNA methyltransferase

DS:

Dyad symmetry

EBER:

Epstein–Barr encoded small RNA

eBL:

Endemically occurring BL

EBNA:

Epstein–Barr nuclear antigen

EBNA-LP:

EBNA-leader protein

EBV:

Epstein–Barr virus

EZH2:

Enhancer of zeste homologue 2

FR:

Family of repeats

GC:

Gastric carcinoma

GC:

Germinal center

GSTP1:

Glutathione S-transferase P1

H3K27me3:

Histone 3 trimethylated on lysine 27

H3K4me2:

Histone 3 dimethylated on lysine 4

H3K4me3:

Histone 3 trimethylated on lysine 4

H3K9me3:

Histone 3 trimethylated on lysine 9

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HDAC:

Histone deacetylase

HHV-8:

Human herpesvirus-8

HL:

Hodgkin’s lymphoma

HP1:

Heterochromatin-associated protein 1

HPV:

Human papillomavirus

HRS:

Hodgkin and Reed–Sternberg cells

HTLV:

Human T-lymphotropic virus

IM:

Infectious mononucleosis

KDM:

Lysine demethylase

KSHV:

Kaposi’s sarcoma herpesvirus

LANA:

Latency-associated nuclear antigen

LCL:

Lymphoblastoid cell line

LCR:

Locus control region or long control region

LINE-1:

Long interspersed element-1

LMP:

Latent membrane protein

LMP2Ap:

LMP2A promoter

lncRNA:

Long noncoding RNA

MCD:

Multicentric Castleman’s disease

MCPyV:

Merkel cell polyomavirus

MeCP2:

Methylcytosine-binding protein 2

MGMT:

O6-methylguanine DNA methyltransferase

miRNA:

MicroRNA

NHL:

Non-Hodgkin lymphoma

NPC:

Nasopharyngeal carcinoma

PAN:

Polyadenylated nuclear RNA

PcG:

Polycomb group

PEL:

Primary effusion lymphoma

PIN:

Prostatic intraepithelial neoplasias

pRB:

Retinoblastoma protein

PRC:

Polycomb repressive complex

PTEN:

Phosphatase and tensin homologue

PTLD:

Posttransplant lymphoproliferative disorder

Qp:

Q promoter

RARβ2:

Retinoic acid receptor β2

RARRES:

Retinoic acid receptor responder

RASSF1A:

RAS association domain family 1 isoform A

sBL:

Sporadic BL

SFRP1:

Secreted frizzled-related protein 1

siRNA:

Short interfering RNA

snoRNA:

Small nucleolar RNA

SOCS:

Suppressor of cytokine signaling

TAg:

T antigen

TR:

Terminal repeat

TrxG:

Trithorax group

Wp:

W promoter

References

  • Anastasiadou, E., Boccellato, F., Vincenti, S., Rosato, P., Bozzoni, I., Frati, L., Faggioni, A., Presutti, C. & Trivedi, P. (2010). Epstein-Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b. Oncogene 29, 1316–1328.

    Article  PubMed  CAS  Google Scholar 

  • Anderton, J. A., Bose, S., Vockerodt, M., Vrzalikova, K., Wei, W., Kuo, M., Helin, K., Christensen, J., Rowe, M., Murray, P. G. & Woodman, C. B. (2011). The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin’s Lymphoma. Oncogene 30, 2037–2043.

    Article  PubMed  CAS  Google Scholar 

  • Araujo, I., Foss, H. D., Hummel, M., Anagnostopoulos, I., Barbosa, H. S., Bittencourt, A. & Stein, H. (1999). Frequent expansion of Epstein-Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV-associated lymphoma. J Pathol 187, 326–330.

    Article  PubMed  CAS  Google Scholar 

  • Arora, P., Kim, E. O., Jung, J. K. & Jang, K. L. (2008). Hepatitis C virus core protein downregulates E-cadherin expression via activation of DNA methyltransferase 1 and 3b. Cancer Lett 261, 244–252.

    Article  PubMed  CAS  Google Scholar 

  • Balassiano, K., Lima, S., Jenab, M., Overvad, K., Tjonneland, A., Boutron-Ruault, M. C., Clavel-Chapelon, F., Canzian, F., Kaaks, R., Boeing, H., Meidtner, K., Trichopoulou, A., Laglou, P., Vineis, P., Panico, S., Palli, D., Grioni, S., Tumino, R., Lund, E., Bueno-de-Mesquita, H. B., Numans, M. E., Peeters, P. H., Ramon, Q. J., Sanchez, M. J., Navarro, C., Ardanaz, E., Dorronsoro, M., Hallmans, G., Stenling, R., Ehrnstrom, R., Regner, S., Allen, N. E., Travis, R. C., Khaw, K. T., Offerhaus, G. J., Sala, N., Riboli, E., Hainaut, P., Scoazec, J. Y., Sylla, B. S., Gonzalez, C. A. & Herceg, Z. (2011). Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Cancer Lett 311, 85–95.

    Article  PubMed  CAS  Google Scholar 

  • Baudouin, V., Dehee, A., Pedron-Grossetete, B., Ansart-Pirenne, H., Haddad, E., Maisin, A., Loirat, C. & Sterkers, G. (2004). Relationship between CD8+ T-cell phenotype and function, Epstein-Barr virus load, and clinical outcome in pediatric renal transplant recipients: a prospective study. Transplantation 77, 1706–1713.

    Article  PubMed  Google Scholar 

  • Baylin, S. B. & Herman, J. G. (2000). Epigenetics and loss of gene function in cancer. In DNA Alterations in Cancer, pp. 293–309. Edited by M. Ehrlich. Westborough: Eaton Publishing.

    Google Scholar 

  • Bekkers, R. L., van der Avoort, I., Melchers, W. J., Bulten, J., de Wilde, P. C. & Massuger, L. F. (2005). Down regulation of estrogen receptor expression is an early event in human papillomavirus infected cervical dysplasia. Eur J Gynaecol Oncol 26, 376–382.

    PubMed  CAS  Google Scholar 

  • Bellan, C., Lazzi, S., Hummel, M., Palummo, N., de Santi, M., Amato, T., Nyagol, J., Sabattini, E., Lazure, T., Pileri, S. A., Raphael, M., Stein, H., Tosi, P. & Leoncini, L. (2005). Immunoglobulin gene analysis reveals 2 distinct cells of origin for EBV-positive and EBV-negative Burkitt lymphomas. Blood 106, 1031–1036.

    Article  PubMed  CAS  Google Scholar 

  • Bieging, K. T., Fish, K., Bondada, S. & Longnecker, R. (2011). A shared gene expression signature in mouse models of EBV-associated and non-EBV-associated Burkitt’s lymphoma. Blood 118, 6849–6859.

    Google Scholar 

  • Blomen, V. A. & Boonstra, J. (2011). Stable transmission of reversible modifications: maintenance of epigenetic information through the cell cycle. Cell Mol Life Sci 68, 27–44.

    Article  PubMed  CAS  Google Scholar 

  • Bonati, M. T., Asselta, R., Duga, S., Ferini-Strambi, L., Oldani, A., Zucconi, M., Malcovati, M., Dalpra, L. & Tenchini, M. L. (2000). Refined mapping of CHRNA3/A5/B4 gene cluster and its implications in ADNFLE. Neuroreport 11, 2097–2101.

    Article  PubMed  CAS  Google Scholar 

  • Bossuyt, W., De Geest, N., Aerts, S., Leenaerts, I., Marynen, P. & Hassan, B. A. (2009a). The atonal proneural transcription factor links differentiation and tumor formation in Drosophila. PLoS Biol 7, e40.

    Article  PubMed  CAS  Google Scholar 

  • Bossuyt, W., Kazanjian, A., De Geest, N., Van Kelst, S., De Hertogh, G., Geboes, K., Boivin, G. P., Luciani, J., Fuks, F., Chuah, M., Van den Driessche, T., Marynen, P., Cools, J., Shroyer, N. F. & Hassan, B. A. (2009b). Atonal homolog 1 is a tumor suppressor gene. PLoS Biol 7, e39.

    Article  PubMed  CAS  Google Scholar 

  • Brauninger, A., Spieker, T., Mottok, A., Baur, A. S., Kuppers, R. & Hansmann, M. L. (2003). Epstein-Barr virus (EBV)-positive lymphoproliferations in post-transplant patients show immunoglobulin V gene mutation patterns suggesting interference of EBV with normal B cell differentiation processes. Eur J Immunol 33, 1593–1602.

    Article  PubMed  CAS  Google Scholar 

  • Brink, A. A., Dukers, D. F., van Den Brule, A. J., Oudejans, J. J., Middeldorp, J. M., Meijer, C. J. & Jiwa, M. (1997). Presence of Epstein-Barr virus latency type III at the single cell level in post-transplantation lymphoproliferative disorders and AIDS related lymphomas. J Clin Pathol 50, 911–918.

    Article  PubMed  CAS  Google Scholar 

  • Burgers, W. A., Blanchon, L., Pradhan, S., de Launoit, Y., Kouzarides, T. & Fuks, F. (2007). Viral oncoproteins target the DNA methyltransferases. Oncogene 26, 1650–1655.

    Article  PubMed  CAS  Google Scholar 

  • Burkitt, D. (1958). A sarcoma involving the jaws in African children. Br J Surg 45, 218–223.

    Article  Google Scholar 

  • Burkitt, D. (1962). A children’s cancer dependent upon climatic factors. Nature 194, 232–234.

    Article  PubMed  CAS  Google Scholar 

  • Calvanese, V., Fernandez, A. F., Urdinguio, R. G., Suarez-Alvarez, B., Mangas, C., Perez-Garcia, V., Bueno, C., Montes, R., Ramos-Mejia, V., Martinez-Camblor, P., Ferrero, C., Assenov, Y., Bock, C., Menendez, P., Carrera, A. C., Lopez-Larrea, C. & Fraga, M. F. (2012). A promoter DNA demethylation landscape of human hematopoietic differentiation. Nucleic Acids Res 40, 116–131.

    Google Scholar 

  • Cameron, J. E., Yin, Q., Fewell, C., Lacey, M., McBride, J., Wang, X., Lin, Z., Schaefer, B. C. & Flemington, E. K. (2008). Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol 82, 1946–1958.

    Article  PubMed  CAS  Google Scholar 

  • Carbone, A., Cilia, A. M., Gloghini, A., Capello, D., Fassone, L., Perin, T., Rossi, D., Canzonieri, V., De Paoli, P., Vaccher, E., Tirelli, U., Volpe, R. & Gaidano, G. (2000). Characterization of a novel HHV-8-positive cell line reveals implications for the pathogenesis and cell cycle control of primary effusion lymphoma. Leukemia 14, 1301–1309.

    Article  PubMed  CAS  Google Scholar 

  • Cazalla, D., Yario, T. & Steitz, J. A. (2010). Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA. Science 328, 1563–1566.

    Article  PubMed  CAS  Google Scholar 

  • Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J. & Zoghbi, H. Y. (2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320, 1224–1229.

    Article  PubMed  CAS  Google Scholar 

  • Chang, C. F., Wang, M., Fang, C. Y., Chen, P. L., Wu, S. F., Chan, M. W. & Chang, D. (2011). Analysis of DNA methylation in human BK virus. Virus Genes 43, 201–207.

    Article  PubMed  CAS  Google Scholar 

  • Chang, Y., Cesarman, E., Pessin, M. S., Lee, F., Culpepper, J., Knowles, D. M. & Moore, P. S. (1994). Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266, 1865–1869.

    Article  PubMed  CAS  Google Scholar 

  • Chau, C. M. & Lieberman, P. M. (2004). Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. J Virol 78, 12308–12319.

    Article  PubMed  CAS  Google Scholar 

  • Chinnasri, P., Pairojkul, C., Jearanaikoon, P., Sripa, B., Bhudhisawasdi, V., Tantimavanich, S. & Limpaiboon, T. (2009). Preferentially different mechanisms of inactivation of 9p21 gene cluster in liver fluke-related cholangiocarcinoma. Hum Pathol 40, 817–826.

    Article  PubMed  CAS  Google Scholar 

  • Cotter, M. A. & Robertson, E. S. (2000). Modulation of histone acetyltransferase activity through interaction of epstein-barr nuclear antigen 3C with prothymosin alpha. Mol Cell Biol 20, 5722–5735.

    Article  PubMed  CAS  Google Scholar 

  • Dave, S. S., Fu, K., Wright, G. W., Lam, L. T., Kluin, P., Boerma, E. J., Greiner, T. C., Weisenburger, D. D., Rosenwald, A., Ott, G., Muller-Hermelink, H. K., Gascoyne, R. D., Delabie, J., Rimsza, L. M., Braziel, R. M., Grogan, T. M., Campo, E., Jaffe, E. S., Dave, B. J., Sanger, W., Bast, M., Vose, J. M., Armitage, J. O., Connors, J. M., Smeland, E. B., Kvaloy, S., Holte, H., Fisher, R. I., Miller, T. P., Montserrat, E., Wilson, W. H., Bahl, M., Zhao, H., Yang, L., Powell, J., Simon, R., Chan, W. C. & Staudt, L. M. (2006). Molecular diagnosis of Burkitt’s lymphoma. N Engl J Med 354, 2431–2442.

    Article  PubMed  CAS  Google Scholar 

  • Davis, J. E., Sherritt, M. A., Bharadwaj, M., Morrison, L. E., Elliott, S. L., Kear, L. M., Maddicks-Law, J., Kotsimbos, T., Gill, D., Malouf, M., Falk, M. C., Khanna, R. & Moss, D. J. (2004). Determining virological, serological and immunological parameters of EBV infection in the development of PTLD. Int Immunol 16, 983–989.

    Article  PubMed  CAS  Google Scholar 

  • Day, L., Chau, C. M., Nebozhyn, M., Rennekamp, A. J., Showe, M. & Lieberman, P. M. (2007). Chromatin profiling of Epstein-Barr virus latency control region. J Virol 81, 6389–6401.

    Article  PubMed  CAS  Google Scholar 

  • De Castro Arce, J., Gockel-Krzikalla, E. & Rosl, F. (2007). Retinoic acid receptor beta silences human papillomavirus-18 oncogene expression by induction of de novo methylation and heterochromatinization of the viral control region. J Biol Chem 282, 28520–28529.

    Article  CAS  Google Scholar 

  • De la Cruz-Hernandez, E., Perez-Plasencia, C., Perez-Cardenas, E., Gonzalez-Fierro, A., Trejo-Becerril, C., Chavez-Blanco, A., Taja-Chayeb, L., Vidal, S., Gutierrez, O., Dominguez, G. I., Trujillo, J. E. & Duenas-Gonzalez, A. (2011). Transcriptional changes induced by epigenetic therapy with hydralazine and magnesium valproate in cervical carcinoma. Oncol Rep 25, 399–407.

    PubMed  Google Scholar 

  • Degner, S. C., Wong, T. P., Jankevicius, G. & Feeney, A. J. (2009). Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development. J Immunol 182, 44–48.

    PubMed  CAS  Google Scholar 

  • Dinand, V. & Arya, L. S. (2006). Epidemiology of childhood Hodgkin’s disease: is it different in developing countries? Indian Pediatr 43, 141–147.

    PubMed  Google Scholar 

  • Dong, S. M., Kim, H. S., Rha, S. H. & Sidransky, D. (2001). Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix. Clin Cancer Res 7, 1982–1986.

    PubMed  CAS  Google Scholar 

  • Donninger, H., Vos, M. D. & Clark, G. J. (2007). The RASSF1A tumor suppressor. J Cell Sci 120, 3163–3172.

    Article  PubMed  CAS  Google Scholar 

  • Duensing, S. & Munger, K. (2003). Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members. J Virol 77, 12331–12335.

    Article  PubMed  CAS  Google Scholar 

  • Duong, F. H., Christen, V., Filipowicz, M. & Heim, M. H. (2006). S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro. Hepatology 43, 796–806.

    Article  PubMed  CAS  Google Scholar 

  • Dutton, A., Woodman, C. B., Chukwuma, M. B., Last, J. I., Wei, W., Vockerodt, M., Baumforth, K. R., Flavell, J. R., Rowe, M., Taylor, A. M., Young, L. S. & Murray, P. G. (2007). Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells. Blood 109, 2597–2603.

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich, M. (2000). DNA hypomethylation and cancer. In DNA Alterations in Cancer, pp. 273–291. Edited by M. Ehrlich. Westborough: Eaton Publishing.

    Google Scholar 

  • Epstein, M. A., Achong, B. G. & Barr, Y. M. (1964). Virus particles in cultured lymphoblasts from Burkitt’s Lymphoma. Lancet 1, 702–703.

    Article  PubMed  CAS  Google Scholar 

  • Feng, H., Shuda, M., Chang, Y. & Moore, P. S. (2008). Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319, 1096–1100.

    Article  PubMed  CAS  Google Scholar 

  • Feng, Q., Stern, J. E., Hawes, S. E., Lu, H., Jiang, M. & Kiviat, N. B. (2010). DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infection. Exp Mol Pathol 88, 287–292.

    Article  PubMed  CAS  Google Scholar 

  • Fernandez, A. F., Rosales, C., Lopez-Nieva, P., Grana, O., Ballestar, E., Ropero, S., Espada, J., Melo, S. A., Lujambio, A., Fraga, M. F., Pino, I., Javierre, B., Carmona, F. J., Acquadro, F., Steenbergen, R. D., Snijders, P. J., Meijer, C. J., Pineau, P., Dejean, A., Lloveras, B., Capella, G., Quer, J., Buti, M., Esteban, J. I., Allende, H., Rodriguez-Frias, F., Castellsague, X., Minarovits, J., Ponce, J., Capello, D., Gaidano, G., Cigudosa, J. C., Gomez-Lopez, G., Pisano, D. G., Valencia, A., Piris, M. A., Bosch, F. X., Cahir-McFarland, E., Kieff, E. & Esteller, M. (2009). The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Res 19, 438–451.

    Article  PubMed  CAS  Google Scholar 

  • Flatley, J. E., McNeir, K., Balasubramani, L., Tidy, J., Stuart, E. L., Young, T. A. & Powers, H. J. (2009). Folate status and aberrant DNA methylation are associated with HPV infection and cervical pathogenesis. Cancer Epidemiol Biomarkers Prev 18, 2782–2789.

    Article  PubMed  CAS  Google Scholar 

  • Formeister, E. J., Tsuchiya, M., Fujii, H., Shpyleva, S., Pogribny, I. P. & Rusyn, I. (2010). Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma. Mutat Res 692, 26–33.

    Article  PubMed  CAS  Google Scholar 

  • Fukayama, M., Hino, R. & Uozaki, H. (2008). Epstein-Barr virus and gastric carcinoma: virus-host interactions leading to carcinoma. Cancer Sci 99, 1726–1733.

    Article  PubMed  CAS  Google Scholar 

  • Gatto, G., Rossi, A., Rossi, D., Kroening, S., Bonatti, S. & Mallardo, M. (2008). Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res 36, 6608–6619.

    Article  PubMed  CAS  Google Scholar 

  • Gatza, M. L., Chandhasin, C., Ducu, R. I. & Marriott, S. J. (2005). Impact of transforming viruses on cellular mutagenesis, genome stability, and cellular transformation. Environ Mol Mutagen 45, 304–325.

    Article  PubMed  CAS  Google Scholar 

  • Goossens, T., Klein, U. & Kuppers, R. (1998). Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci U S A 95, 2463–2468.

    Article  PubMed  CAS  Google Scholar 

  • Gottschalk, S., Rooney, C. M. & Heslop, H. E. (2005). Post-transplant lymphoproliferative disorders. Annu Rev Med 56, 29–44.

    Article  PubMed  CAS  Google Scholar 

  • Grogg, K. L., Miller, R. F. & Dogan, A. (2007). HIV infection and lymphoma. J Clin Pathol 60, 1365–1372.

    Article  PubMed  CAS  Google Scholar 

  • Gunther, T. & Grundhoff, A. (2010). The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes. PLoS Pathog 6, e1000935.

    Article  PubMed  CAS  Google Scholar 

  • Gupta, R. A., Shah, N., Wang, K. C., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M. C., Hung, T., Argani, P., Rinn, J. L., Wang, Y., Brzoska, P., Kong, B., Li, R., West, R. B., van de Vijver, M. J., Sukumar, S. & Chang, H. Y. (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464, 1071–1076.

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez, M. I., Siraj, A. K., Khaled, H., Koon, N., El Rifai, W. & Bhatia, K. (2004). CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer. Mod Pathol 17, 1268–1274.

    Article  PubMed  CAS  Google Scholar 

  • Hansen, J. C., Ghosh, R. P. & Woodcock, C. L. (2010). Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin. IUBMB Life 62, 732–738.

    Article  PubMed  CAS  Google Scholar 

  • Hansen, K. D., Timp, W., Bravo, H. C., Sabunciyan, S., Langmead, B., McDonald, O. G., Wen, B., Wu, H., Liu, Y., Diep, D., Briem, E., Zhang, K., Irizarry, R. A. & Feinberg, A. P. (2011). Increased methylation variation in epigenetic domains across cancer types. Nat Genet 43, 768–775.

    Article  PubMed  CAS  Google Scholar 

  • He, Y. F., Li, B. Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C. X., Zhang, K., He, C. & Xu, G. L. (2011). Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333, 1303–1307.

    Article  PubMed  CAS  Google Scholar 

  • Hecht, J. L. & Aster, J. C. (2000). Molecular biology of Burkitt’s lymphoma. J Clin Oncol 18, 3707–3721.

    PubMed  CAS  Google Scholar 

  • Helmbold, P., Lahtz, C., Enk, A., Herrmann-Trost, P., Marsch, W. C., Kutzner, H. & Dammann, R. H. (2009). Frequent occurrence of RASSF1A promoter hypermethylation and Merkel cell polyomavirus in Merkel cell carcinoma. Mol Carcinog 48, 903–909.

    Article  PubMed  CAS  Google Scholar 

  • Helt, A. M. & Galloway, D. A. (2003). Mechanisms by which DNA tumor virus oncoproteins target the Rb family of pocket proteins. Carcinogenesis 24, 159–169.

    Article  PubMed  CAS  Google Scholar 

  • Henken, F. E., Wilting, S. M., Overmeer, R. M., van Rietschoten, J. G., Nygren, A. O., Errami, A., Schouten, J. P., Meijer, C. J., Snijders, P. J. & Steenbergen, R. D. (2007). Sequential gene promoter methylation during HPV-induced cervical carcinogenesis. Br J Cancer 97, 1457–1464.

    Article  PubMed  CAS  Google Scholar 

  • Herbst, H., Dallenbach, F., Hummel, M., Niedobitek, G., Pileri, S., Muller-Lantzsch, N. & Stein, H. (1991). Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci U S A 88, 4766–4770.

    Article  PubMed  CAS  Google Scholar 

  • Higgs, M. R., Lerat, H. & Pawlotsky, J. M. (2010). Downregulation of Gadd45beta expression by hepatitis C virus leads to defective cell cycle arrest. Cancer Res 70, 4901–4911.

    Article  PubMed  CAS  Google Scholar 

  • Hino, R., Uozaki, H., Murakami, N., Ushiku, T., Shinozaki, A., Ishikawa, S., Morikawa, T., Nakaya, T., Sakatani, T., Takada, K. & Fukayama, M. (2009). Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res 69, 2766–2774.

    Article  PubMed  CAS  Google Scholar 

  • Hjalgrim, H., Askling, J., Rostgaard, K., Hamilton-Dutoit, S., Frisch, M., Zhang, J. S., Madsen, M., Rosdahl, N., Konradsen, H. B., Storm, H. H. & Melbye, M. (2003). Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med 349, 1324–1332.

    Article  PubMed  CAS  Google Scholar 

  • Hjalgrim, H. & Engels, E. A. (2008). Infectious aetiology of Hodgkin and non-Hodgkin lymphomas: a review of the epidemiological evidence. J Intern Med 264, 537–548.

    Article  PubMed  CAS  Google Scholar 

  • Holland, D., Hoppe-Seyler, K., Schuller, B., Lohrey, C., Maroldt, J., Durst, M. & Hoppe-Seyler, F. (2008). Activation of the enhancer of zeste homologue 2 gene by the human papillomavirus E7 oncoprotein. Cancer Res 68, 9964–9972.

    Article  PubMed  CAS  Google Scholar 

  • Howie, H. L., Katzenellenbogen, R. A. & Galloway, D. A. (2009). Papillomavirus E6 proteins. Virology 384, 324–334.

    Article  PubMed  CAS  Google Scholar 

  • Hsu, C. H., Peng, K. L., Jhang, H. C., Lin, C. H., Wu, S. Y., Chiang, C. M., Lee, S. C., Yu, W. C. & Juan, L. J. (2011). The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription. Oncogene. doi: 10.1038/onc.2011.415.

    Google Scholar 

  • Hu, J., Dong, A., Fernandez-Ruiz, V., Shan, J., Kawa, M., Martinez-Anso, E., Prieto, J. & Qian, C. (2009). Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res 69, 6951–6959.

    Article  PubMed  CAS  Google Scholar 

  • Hummel, M., Bentink, S., Berger, H., Klapper, W., Wessendorf, S., Barth, T. F., Bernd, H. W., Cogliatti, S. B., Dierlamm, J., Feller, A. C., Hansmann, M. L., Haralambieva, E., Harder, L., Hasenclever, D., Kuhn, M., Lenze, D., Lichter, P., Martin-Subero, J. I., Moller, P., Muller-Hermelink, H. K., Ott, G., Parwaresch, R. M., Pott, C., Rosenwald, A., Rosolowski, M., Schwaenen, C., Sturzenhofecker, B., Szczepanowski, M., Trautmann, H., Wacker, H. H., Spang, R., Loeffler, M., Trumper, L., Stein, H. & Siebert, R. (2006). A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med 354, 2419–2430.

    Article  PubMed  CAS  Google Scholar 

  • Hung, T. & Chang, H. Y. (2010). Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol 7, 582–585.

    Article  PubMed  CAS  Google Scholar 

  • Hutzinger, R., Feederle, R., Mrazek, J., Schiefermeier, N., Balwierz, P. J., Zavolan, M., Polacek, N., Delecluse, H. J. & Huttenhofer, A. (2009). Expression and processing of a small nucleolar RNA from the Epstein-Barr virus genome. PLoS Pathog 5, e1000547.

    Article  PubMed  CAS  Google Scholar 

  • Hyland, P. L., McDade, S. S., McCloskey, R., Dickson, G. J., Arthur, K., McCance, D. J. & Patel, D. (2011). Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes. J Virol 85, 10999–11006.

    Article  PubMed  CAS  Google Scholar 

  • Iaquinta, P. J. & Lees, J. A. (2007). Life and death decisions by the E2F transcription factors. Curr Opin Cell Biol 19, 649–657.

    Article  PubMed  CAS  Google Scholar 

  • Issa, J. P. (2011). Epigenetic variation and cellular Darwinism. Nat Genet 43, 724–726.

    Article  PubMed  CAS  Google Scholar 

  • Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C. & Zhang, Y. (2011). Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300–1303.

    Article  PubMed  CAS  Google Scholar 

  • Janas, J. A. & Van Aelst, L. (2011). Oncogenic tyrosine kinases target Dok-1 for ubiquitin-mediated proteasomal degradation to promote cell transformation. Mol Cell Biol 31, 2552–2565.

    Article  PubMed  CAS  Google Scholar 

  • Jarrett, R. F. (2003). Risk factors for Hodgkin’s lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin’s lymphoma. Leuk Lymphoma 44 Suppl 3, S27–S32.

    Article  PubMed  CAS  Google Scholar 

  • Kamdar, K. Y., Rooney, C. M. & Heslop, H. E. (2011). Posttransplant lymphoproliferative disease following liver transplantation. Curr Opin Organ Transplant 16, 274–280.

    Article  PubMed  CAS  Google Scholar 

  • Kang, G. H., Lee, S., Cho, N. Y., Gandamihardja, T., Long, T. I., Weisenberger, D. J., Campan, M. & Laird, P. W. (2008). DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest 88, 161–170.

    Article  PubMed  CAS  Google Scholar 

  • Kang, H., Wiedmer, A., Yuan, Y., Robertson, E. & Lieberman, P. M. (2011). Coordination of KSHV latent and lytic gene control by CTCF-cohesin mediated chromosome conformation. PLoS Pathog 7, e1002140.

    Article  PubMed  CAS  Google Scholar 

  • Katoh, H., Shibata, T., Kokubu, A., Ojima, H., Fukayama, M., Kanai, Y. & Hirohashi, S. (2006). Epigenetic instability and chromosomal instability in hepatocellular carcinoma. Am J Pathol 168, 1375–1384.

    Article  PubMed  CAS  Google Scholar 

  • Kaur, P., Paliwal, A., Durantel, D., Hainaut, P., Scoazec, J. Y., Zoulim, F., Chemin, I. & Herceg, Z. (2010). DNA methylation of hepatitis B virus (HBV) genome associated with the development of hepatocellular carcinoma and occult HBV infection. J Infect Dis 202, 700–704.

    Article  PubMed  CAS  Google Scholar 

  • Kelly, G., Bell, A. & Rickinson, A. (2002). Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2. Nat Med 8, 1098–1104.

    Article  PubMed  CAS  Google Scholar 

  • Kimura, H., Nakamura, T., Ogawa, T., Tanaka, S. & Shiota, K. (2003). Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. Nucleic Acids Res 31, 3101–3113.

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita, T., Nomoto, S., Kodera, Y., Koike, M., Fujiwara, M. & Nakao, A. (2011). Decreased expression and aberrant hypermethylation of the SFRP genes in human gastric cancer. Hepatogastroenterology 58, 1051–1056.

    Article  PubMed  Google Scholar 

  • Kitkumthorn, N., Yanatatsanajit, P., Kiatpongsan, S., Phokaew, C., Triratanachat, S., Trivijitsilp, P., Termrungruanglert, W., Tresukosol, D., Niruthisard, S. & Mutirangura, A. (2006). Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer. BMC Cancer 6:55.

    Article  PubMed  CAS  Google Scholar 

  • Knight, J. S., Lan, K., Subramanian, C. & Robertson, E. S. (2003). Epstein-Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines. J Virol 77, 4261–4272.

    Article  PubMed  CAS  Google Scholar 

  • Ko, E., Kim, S. J., Joh, J. W., Park, C. K., Park, J. & Kim, D. H. (2008). CpG island hypermethylation of SOCS-1 gene is inversely associated with HBV infection in hepatocellular carcinoma. Cancer Lett 271, 240–250.

    Article  PubMed  CAS  Google Scholar 

  • Kohno, T., Kunitoh, H., Mimaki, S., Shiraishi, K., Kuchiba, A., Yamamoto, S. & Yokota, J. (2011). Contribution of the TP53, OGG1, CHRNA3, and HLA-DQA1 genes to the risk for lung squamous cell carcinoma. J Thorac Oncol 6, 813–817.

    Article  PubMed  Google Scholar 

  • Kremer, B. E., Reshef, R., Misleh, J. G., Christie, J. D., Ahya, V. N., Blumenthal, N. P., Kotloff, R. M., Hadjiliadis, D., Stadtmauer, E. A., Schuster, S. J. & Tsai, D. E. (2011). Post-transplant lymphoproliferative disorder after lung transplantation: A review of 35 cases. J Heart Lung Transplant 31, 296–304.

    Google Scholar 

  • Krishna, S. M., Kattoor, J. & Balaram, P. (2005). Down regulation of adhesion protein E-cadherin in Epstein-Barr virus infected nasopharyngeal carcinomas. Cancer Biomark 1, 271–277.

    PubMed  CAS  Google Scholar 

  • Krithivas, A., Young, D. B., Liao, G., Greene, D. & Hayward, S. D. (2000). Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein-Barr virus gene expression in dually infected PEL cells. J Virol 74, 9637–9645.

    Article  PubMed  CAS  Google Scholar 

  • Kuppers, R. (2009). The biology of Hodgkin’s lymphoma. Nat Rev Cancer 9, 15–27.

    Article  PubMed  CAS  Google Scholar 

  • Kuppers, R., Klein, U., Schwering, I., Distler, V., Brauninger, A., Cattoretti, G., Tu, Y., Stolovitzky, G. A., Califano, A., Hansmann, M. L. & Dalla-Favera, R. (2003). Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. J Clin Invest 111, 529–537.

    PubMed  CAS  Google Scholar 

  • Kuppers, R., Schwering, I., Brauninger, A., Rajewsky, K. & Hansmann, M. L. (2002). Biology of Hodgkin’s lymphoma. Ann Oncol 13 Suppl 1, 11–18.

    Article  PubMed  Google Scholar 

  • Kurth, J., Hansmann, M. L., Rajewsky, K. & Kuppers, R. (2003). Epstein-Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction. Proc Natl Acad Sci U S A 100, 4730–4735.

    Article  PubMed  CAS  Google Scholar 

  • Kwong, J., Lo, K. W., Chow, L. S., Chan, F. L., To, K. F. & Huang, D. P. (2005a). Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma. Int J Cancer 113, 386–392.

    Article  PubMed  CAS  Google Scholar 

  • Kwong, J., Lo, K. W., Chow, L. S., To, K. F., Choy, K. W., Chan, F. L., Mok, S. C. & Huang, D. P. (2005b). Epigenetic silencing of cellular retinol-binding proteins in nasopharyngeal carcinoma. Neoplasia 7, 67–74.

    Article  PubMed  CAS  Google Scholar 

  • Kwong, J., Lo, K. W., To, K. F., Teo, P. M., Johnson, P. J. & Huang, D. P. (2002). Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. Clin Cancer Res 8, 131–137.

    PubMed  CAS  Google Scholar 

  • Lai, H. C., Lin, Y. W., Huang, R. L., Chung, M. T., Wang, H. C., Liao, Y. P., Su, P. H., Liu, Y. L. & Yu, M. H. (2010). Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse. Cancer 116, 4266–4274.

    Article  PubMed  CAS  Google Scholar 

  • Lai, H. C., Lin, Y. W., Huang, T. H., Yan, P., Huang, R. L., Wang, H. C., Liu, J., Chan, M. W., Chu, T. Y., Sun, C. A., Chang, C. C. & Yu, M. H. (2008). Identification of novel DNA methylation markers in cervical cancer. Int J Cancer 123, 161–167.

    Article  PubMed  CAS  Google Scholar 

  • Lambert, M. P., Paliwal, A., Vaissiere, T., Chemin, I., Zoulim, F., Tommasino, M., Hainaut, P., Sylla, B., Scoazec, J. Y., Tost, J. & Herceg, Z. (2011). Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake. J Hepatol 54, 705–715.

    Article  PubMed  CAS  Google Scholar 

  • Laurent-Puig, P. & Zucman-Rossi, J. (2006). Genetics of hepatocellular tumors. Oncogene 25, 3778–3786.

    Article  PubMed  CAS  Google Scholar 

  • Lee, T. S., Kim, J. W., Kang, G. H., Park, N. H., Song, Y. S., Kang, S. B. & Lee, H. P. (2006). DNA hypomethylation of CAGE promotors in squamous cell carcinoma of uterine cervix. Ann N Y Acad Sci 1091, 218–224.

    Article  PubMed  CAS  Google Scholar 

  • Lenze, D., Leoncini, L., Hummel, M., Volinia, S., Liu, C. G., Amato, T., De Falco, G., Githanga, J., Horn, H., Nyagol, J., Ott, G., Palatini, J., Pfreundschuh, M., Rogena, E., Rosenwald, A., Siebert, R., Croce, C. M. & Stein, H. (2011). The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma. Leukemia 25, 1869–1876.

    Google Scholar 

  • Leonard, S., Wei, W., Anderton, J., Vockerodt, M., Rowe, M., Murray, P. G. & Woodman, C. B. (2011). Epigenetic and transcriptional changes which follow Epstein-Barr virus infection of germinal center B cells and their relevance to the pathogenesis of Hodgkin’s lymphoma. J Virol 85, 9568–9577.

    Article  PubMed  CAS  Google Scholar 

  • Levens, D. L. (2003). Reconstructing MYC. Genes Dev 17, 1071–1077.

    Article  PubMed  CAS  Google Scholar 

  • Li, G., Wu, Z., Peng, Y., Liu, X., Lu, J., Wang, L., Pan, Q., He, M. L. & Li, X. P. (2010). MicroRNA-10b induced by Epstein-Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells. Cancer Lett 299, 29–36.

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Hui, A. M., Sun, L., Hasegawa, K., Torzilli, G., Minagawa, M., Takayama, T. & Makuuchi, M. (2004). p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma. Clin Cancer Res 10, 7484–7489.

    Article  PubMed  CAS  Google Scholar 

  • Lim, C., Lee, D., Seo, T., Choi, C. & Choe, J. (2003). Latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus functionally interacts with heterochromatin protein 1. J Biol Chem 278, 7397–7405.

    Article  PubMed  CAS  Google Scholar 

  • Lin, I. G., Tomzynski, T. J., Ou, Q. & Hsieh, C. L. (2000). Modulation of DNA binding protein affinity directly affects target site demethylation. Mol Cell Biol 20, 2343–2349.

    Article  PubMed  CAS  Google Scholar 

  • Ling, P. D., Tan, J. & Peng, R. (2009). Nuclear-cytoplasmic shuttling is not required for the Epstein-Barr virus EBNA-LP transcriptional coactivation function. J Virol 83, 7109–7116.

    Article  PubMed  CAS  Google Scholar 

  • Liu, L., Tommasi, S., Lee, D. H., Dammann, R. & Pfeifer, G. P. (2003). Control of microtubule stability by the RASSF1A tumor suppressor. Oncogene 22, 8125–8136.

    Article  PubMed  CAS  Google Scholar 

  • Lo, A. K., To, K. F., Lo, K. W., Lung, R. W., Hui, J. W., Liao, G. & Hayward, S. D. (2007). Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A 104, 16164–16169.

    Article  PubMed  CAS  Google Scholar 

  • Lupberger, J. & Hildt, E. (2007). Hepatitis B virus-induced oncogenesis. World J Gastroenterol 13, 74–81.

    PubMed  CAS  Google Scholar 

  • Machida, K., Cheng, K. T., Sung, V. M., Shimodaira, S., Lindsay, K. L., Levine, A. M., Lai, M. Y. & Lai, M. M. (2004). Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci U S A 101, 4262–4267.

    Article  PubMed  CAS  Google Scholar 

  • Magrath, I., Jain, V. & Bhatia, K. (1992). Epstein-Barr virus and Burkitt’s lymphoma. Semin Cancer Biol 3, 285–295.

    PubMed  CAS  Google Scholar 

  • Martin-Subero, J. I., Kreuz, M., Bibikova, M., Bentink, S., Ammerpohl, O., Wickham-Garcia, E., Rosolowski, M., Richter, J., Lopez-Serra, L., Ballestar, E., Berger, H., Agirre, X., Bernd, H. W., Calvanese, V., Cogliatti, S. B., Drexler, H. G., Fan, J. B., Fraga, M. F., Hansmann, M. L., Hummel, M., Klapper, W., Korn, B., Kuppers, R., Macleod, R. A., Moller, P., Ott, G., Pott, C., Prosper, F., Rosenwald, A., Schwaenen, C., Schubeler, D., Seifert, M., Sturzenhofecker, B., Weber, M., Wessendorf, S., Loeffler, M., Trumper, L., Stein, H., Spang, R., Esteller, M., Barker, D., Hasenclever, D. & Siebert, R. (2009). New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling. Blood 113, 2488–2497.

    Article  PubMed  CAS  Google Scholar 

  • Massari, M. E., Rivera, R. R., Voland, J. R., Quong, M. W., Breit, T. M., van Dongen, J. J., de Smit, O. & Murre, C. (1998). Characterization of ABF-1, a novel basic helix-loop-helix transcription factor expressed in activated B lymphocytes. Mol Cell Biol 18, 3130–3139.

    PubMed  CAS  Google Scholar 

  • Matsumura, S., Persson, L. M., Wong, L. & Wilson, A. C. (2010). The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains. J Virol 84, 2318–2330.

    Article  PubMed  CAS  Google Scholar 

  • Mattsson, K., Kiss, C., Platt, G. M., Simpson, G. R., Kashuba, E., Klein, G., Schulz, T. F. & Szekely, L. (2002). Latent nuclear antigen of Kaposi’s sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions. J Gen Virol 83, 179–188.

    PubMed  CAS  Google Scholar 

  • McCabe, M. T., Low, J. A., Daignault, S., Imperiale, M. J., Wojno, K. J. & Day, M. L. (2006). Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res 66, 385–392.

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin-Drubin, M. E., Crum, C. P. & Munger, K. (2011). Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming. Proc Natl Acad Sci U S A 108, 2130–2135.

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin-Drubin, M. E. & Munger, K. (2009). The human papillomavirus E7 oncoprotein. Virology 384, 335–344.

    Article  PubMed  CAS  Google Scholar 

  • Meng, Y., Wang, Q. G., Wang, J. X., Zhu, S. T., Jiao, Y., Li, P. & Zhang, S. T. (2011). Epigenetic Inactivation of the SFRP1 Gene in Esophageal Squamous Cell Carcinoma. Dig Dis Sci 56, 3195–3203.

    Google Scholar 

  • Minarovits, J. (2006). Epigenotypes of latent herpesvirus genomes. Curr Top Microbiol Immunol 310, 61–80.

    Article  PubMed  CAS  Google Scholar 

  • Minarovits, J., Hu, L. F., Minarovits-Kormuta, S., Klein, G. & Ernberg, I. (1994). Sequence-specific methylation inhibits the activity of the Epstein-Barr virus LMP 1 and BCR2 enhancer-promoter regions. Virology 200, 661–667.

    Article  PubMed  CAS  Google Scholar 

  • Motsch, N., Pfuhl, T., Mrazek, J., Barth, S. & Grasser, F. A. (2007). Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a. RNA Biol 4, 131–137.

    Article  PubMed  CAS  Google Scholar 

  • Mrazek, J., Kreutmayer, S. B., Grasser, F. A., Polacek, N. & Huttenhofer, A. (2007). Subtractive hybridization identifies novel differentially expressed ncRNA species in EBV-infected human B cells. Nucleic Acids Res 35, e73.

    Article  PubMed  CAS  Google Scholar 

  • Muti, G., Klersy, C., Baldanti, F., Granata, S., Oreste, P., Pezzetti, L., Gatti, M., Gargantini, L., Caramella, M., Mancini, V., Gerna, G. & Morra, E. (2003). Epstein-Barr virus (EBV) load and interleukin-10 in EBV-positive and EBV-negative post-transplant lymphoproliferative disorders. Br J Haematol 122, 927–933.

    Article  PubMed  Google Scholar 

  • Naka, K., Abe, K., Takemoto, K., Dansako, H., Ikeda, M., Shimotohno, K. & Kato, N. (2006). Epigenetic silencing of interferon-inducible genes is implicated in interferon resistance of hepatitis C virus replicon-harboring cells. J Hepatol 44, 869–878.

    Article  PubMed  CAS  Google Scholar 

  • Nakase, K., Cheng, J., Zhu, Q. & Marasco, W. A. (2009). Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells. J Leukoc Biol 85, 165–174.

    Article  PubMed  CAS  Google Scholar 

  • Nan, X., Cross, S. & Bird, A. (1998a). Gene silencing by methyl-CpG-binding proteins. Novartis Found Symp 214, 6–16.

    PubMed  CAS  Google Scholar 

  • Nan, X., Ng, H. H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N. & Bird, A. (1998b). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386–389.

    Article  PubMed  CAS  Google Scholar 

  • Narimatsu, T., Tamori, A., Koh, N., Kubo, S., Hirohashi, K., Yano, Y., Arakawa, T., Otani, S. & Nishiguchi, S. (2004). p16 promoter hypermethylation in human hepatocellular carcinoma with or without hepatitis virus infection. Intervirology 47, 26–31.

    Article  PubMed  CAS  Google Scholar 

  • Niemhom, S., Kitazawa, S., Kitazawa, R., Maeda, S. & Leopairat, J. (2008). Hypermethylation of epithelial-cadherin gene promoter is associated with Epstein-Barr virus in nasopharyngeal carcinoma. Cancer Detect Prev 32, 127–134.

    Article  PubMed  CAS  Google Scholar 

  • Niller, H. H., Salamon, D., Banati, F., Schwarzmann, F., Wolf, H. & Minarovits, J. (2004a). The LCR of EBV makes Burkitt’s lymphoma endemic. Trends Microbiol 12, 495–499.

    Article  PubMed  CAS  Google Scholar 

  • Niller, H. H., Salamon, D., Ilg, K., Koroknai, A., Banati, F., Bauml, G., Rucker, O., Schwarzmann, F., Wolf, H. & Minarovits, J. (2003). The in vivo binding site for oncoprotein c-Myc in the promoter for Epstein-Barr virus (EBV) encoding RNA (EBER) 1 suggests a specific role for EBV in lymphomagenesis. Med Sci Monit 9, HY1–HY9.

    Google Scholar 

  • Niller, H. H., Salamon, D., Ilg, K., Koroknai, A., Banati, F., Schwarzmann, F., Wolf, H. & Minarovits, J. (2004b). EBV-associated neoplasms: alternative pathogenetic pathways. Med Hypotheses 62, 387–391.

    Article  PubMed  CAS  Google Scholar 

  • Niller, H. H., Salamon, D., Rahmann, S., Ilg, K., Koroknai, A., Banati, F., Schwarzmann, F., Wolf, H. & Minarovits, J. (2004c). A 30 kb region of the Epstein-Barr virus genome is colinear with the rearranged human immunoglobulin gene loci: implications for a “ping-pong evolution” model for persisting viruses and their hosts. A review. Acta Microbiol Immunol Hung 51, 469–484.

    Article  CAS  Google Scholar 

  • Niller, H. H., Wolf, H. & Minarovits, J. (2007). Epstein-Barr Virus. In Latency Strategies of Herpesviruses, pp. 154–191. Edited by J. Minarovits, E. Gonczol & T. Valyi-Nagy. New York: Springer.

    Google Scholar 

  • Niller, H. H., Wolf, H. & Minarovits, J. (2008). Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity 41, 298–328.

    Article  PubMed  CAS  Google Scholar 

  • Niller, H. H., Wolf, H. & Minarovits, J. (2009). Epigenetic dysregulation of the host cell genome in Epstein-Barr virus-associated neoplasia. Semin Cancer Biol 19, 158–164.

    Article  PubMed  CAS  Google Scholar 

  • Niller, H. H., Wolf, H. & Minarovits, J. (2011). Viral hit and run-oncogenesis: Genetic and epigenetic scenarios. Cancer Lett 305, 200–217.

    Article  PubMed  CAS  Google Scholar 

  • Pallesen, G., Hamilton-Dutoit, S. J., Rowe, M. & Young, L. S. (1991). Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin’s disease. Lancet 337, 320–322.

    Article  PubMed  CAS  Google Scholar 

  • Pantry, S. N. & Medveczky, P. G. (2009). Epigenetic regulation of Kaposi’s sarcoma-associated herpesvirus replication. Semin Cancer Biol 19, 153–157.

    Article  PubMed  CAS  Google Scholar 

  • Park, I. Y., Sohn, B. H., Yu, E., Suh, D. J., Chung, Y. H., Lee, J. H., Surzycki, S. J. & Lee, Y. I. (2007). Aberrant epigenetic modifications in hepatocarcinogenesis induced by hepatitis B virus X protein. Gastroenterology 132, 1476–1494.

    Article  PubMed  CAS  Google Scholar 

  • Pelengaris, S., Khan, M. & Evan, G. I. (2002). Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 109, 321–334.

    Article  PubMed  CAS  Google Scholar 

  • Piccaluga, P. P., De Falco, G., Kustagi, M., Gazzola, A., Agostinelli, C., Tripodo, C., Leucci, E., Onnis, A., Astolfi, A., Sapienza, M. R., Bellan, C., Lazzi, S., Tumwine, L., Mawanda, M., Ogwang, M., Calbi, V., Formica, S., Califano, A., Pileri, S. A. & Leoncini, L. (2011). Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes. Blood 117, 3596–3608.

    Article  PubMed  CAS  Google Scholar 

  • Platt, G., Carbone, A. & Mittnacht, S. (2002). p16INK4a loss and sensitivity in KSHV associated primary effusion lymphoma. Oncogene 21, 1823–1831.

    Article  PubMed  CAS  Google Scholar 

  • Portal, D., Rosendorff, A. & Kieff, E. (2006). Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4. Proc Natl Acad Sci U S A 103, 19278–19283.

    Article  PubMed  CAS  Google Scholar 

  • Raab-Traub, N. & Flynn, K. (1986). The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell 47, 883–889.

    Article  PubMed  CAS  Google Scholar 

  • Rahadiani, N., Takakuwa, T., Tresnasari, K., Morii, E. & Aozasa, K. (2008). Latent membrane protein-1 of Epstein-Barr virus induces the expression of B-cell integration cluster, a precursor form of microRNA-155, in B lymphoma cell lines. Biochem Biophys Res Commun 377, 579–583.

    Article  PubMed  CAS  Google Scholar 

  • Renne, R., Barry, C., Dittmer, D., Compitello, N., Brown, P. O. & Ganem, D. (2001). Modulation of cellular and viral gene expression by the latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus. J Virol 75, 458–468.

    Article  PubMed  CAS  Google Scholar 

  • Ringrose, L. & Paro, R. (2007). Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development 134, 223–232.

    Article  PubMed  CAS  Google Scholar 

  • Roh, T. Y., Cuddapah, S. & Zhao, K. (2005). Active chromatin domains are defined by acetylation islands revealed by genome-wide mapping. Genes Dev 19, 542–552.

    Article  PubMed  CAS  Google Scholar 

  • Rossetto, C. C. & Pari, G. S. (2011). Kaposi’s Sarcoma-Associated Herpesvirus Noncoding Polyadenylated Nuclear RNA Interacts with Virus- and Host Cell-Encoded Proteins and Suppresses Expression of Genes Involved in Immune Modulation. J Virol 85, 13290–13297.

    Article  PubMed  CAS  Google Scholar 

  • Rossi, D., Gaidano, G., Gloghini, A., Deambrogi, C., Franceschetti, S., Berra, E., Cerri, M., Vendramin, C., Conconi, A., Viglio, A., Muti, G., Oreste, P., Morra, E., Paulli, M., Capello, D. & Carbone, A. (2003). Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas. Br J Haematol 123, 475–478.

    Article  PubMed  CAS  Google Scholar 

  • Rossi, G. & Bonetti, F. (2004). EBV and Burkitt’s lymphoma. N Engl J Med 350, 2621.

    Article  PubMed  CAS  Google Scholar 

  • Roughan, J. E., Torgbor, C. & Thorley-Lawson, D. A. (2010). Germinal center B cells latently infected with Epstein-Barr virus proliferate extensively but do not increase in number. J Virol 84, 1158–1168.

    Article  PubMed  CAS  Google Scholar 

  • Saito, Y., Kanai, Y., Sakamoto, M., Saito, H., Ishii, H. & Hirohashi, S. (2002). Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis. Proc Natl Acad Sci U S A 99, 10060–10065.

    Article  PubMed  CAS  Google Scholar 

  • Sakakibara, S., Ueda, K., Nishimura, K., Do, E., Ohsaki, E., Okuno, T. & Yamanishi, K. (2004). Accumulation of heterochromatin components on the terminal repeat sequence of Kaposi’s sarcoma-associated herpesvirus mediated by the latency-associated nuclear antigen. J Virol 78, 7299–7310.

    Article  PubMed  CAS  Google Scholar 

  • Sakuma, K., Chong, J. M., Sudo, M., Ushiku, T., Inoue, Y., Shibahara, J., Uozaki, H., Nagai, H. & Fukayama, M. (2004). High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer 112, 273–278.

    Article  PubMed  CAS  Google Scholar 

  • Salamon, D., Banati, F., Koroknai, A., Ravasz, M., Szenthe, K., Bathori, Z., Bakos, A., Niller, H. H., Wolf, H. & Minarovits, J. (2009). Binding of CCCTC-binding factor in vivo to the region located between Rep* and C-promoter of Epstein-Barr virus is unaffected by CpG methylation and does not correlate with Cp activity. J Gen Virol.

    Google Scholar 

  • Saulnier, A., Vaissiere, T., Yue, J., Siouda, M., Malfroy, M., Accardi, R., Creveaux, M., Sebastian, S., Shahzad, N., Gheit, T., Hussain, I., Torrente, M., Maffini, F. A., Calabrese, L., Chiesa, F., Cuenin, C., Shukla, R., Fathallah, I., Matos, E., Daudt, A., Koifman, S., Wunsch-Filho, V., Menezes, A. M., Curado, M. P., Zaridze, D., Boffetta, P., Brennan, P., Tommasino, M., Herceg, Z. & Sylla, B. S. (2011). Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers. Int J Cancer 130,2484–2894.

    Google Scholar 

  • Shamay, M., Krithivas, A., Zhang, J. & Hayward, S. D. (2006). Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi’s sarcoma-associated herpesvirus LANA. Proc Natl Acad Sci U S A 103, 14554–14559.

    Article  PubMed  CAS  Google Scholar 

  • Shi, N., Ye, S., Bartlam, M., Yang, M., Wu, J., Liu, Y., Sun, F., Han, X., Peng, X., Qiang, B., Yuan, J. & Rao, Z. (2004). Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain. J Biol Chem 279, 4962–4969.

    Article  PubMed  CAS  Google Scholar 

  • Shikauchi, Y., Saiura, A., Kubo, T., Niwa, Y., Yamamoto, J., Murase, Y. & Yoshikawa, H. (2009). SALL3 interacts with DNMT3A and shows the ability to inhibit CpG island methylation in hepatocellular carcinoma. Mol Cell Biol 29, 1944–1958.

    Article  PubMed  CAS  Google Scholar 

  • Shim, Y. H., Yoon, G. S., Choi, H. J., Chung, Y. H. & Yu, E. (2003). p16 Hypermethylation in the early stage of hepatitis B virus-associated hepatocarcinogenesis. Cancer Lett 190, 213–219.

    Article  PubMed  CAS  Google Scholar 

  • Sriraksa, R., Zeller, C., El Bahrawy, M. A., Dai, W., Daduang, J., Jearanaikoon, P., Chau-In, S., Brown, R. & Limpaiboon, T. (2011). CpG-island methylation study of liver fluke-related cholangiocarcinoma. Br J Cancer 104, 1313–1318.

    Article  PubMed  CAS  Google Scholar 

  • Sriuranpong, V., Mutirangura, A., Gillespie, J. W., Patel, V., Amornphimoltham, P., Molinolo, A. A., Kerekhanjanarong, V., Supanakorn, S., Supiyaphun, P., Rangdaeng, S., Voravud, N. & Gutkind, J. S. (2004). Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays. Clin Cancer Res 10, 4944–4958.

    Article  PubMed  CAS  Google Scholar 

  • Staudt, L. M. & Dave, S. (2005). The biology of human lymphoid malignancies revealed by gene expression profiling. Adv Immunol 87, 163–208.

    Article  PubMed  CAS  Google Scholar 

  • Stedman, W., Deng, Z., Lu, F. & Lieberman, P. M. (2004). ORC, MCM, and histone hyperacetylation at the Kaposi’s sarcoma-associated herpesvirus latent replication origin. J Virol 78, 12566–12575.

    Article  PubMed  CAS  Google Scholar 

  • Stevens, S. J., Verschuuren, E. A., Pronk, I., van Der Bij W., Harmsen, M. C., The, T. H., Meijer, C. J., van Den Brule, A. J. & Middeldorp, J. M. (2001). Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood 97, 1165–1171.

    Article  PubMed  CAS  Google Scholar 

  • Stuber, G., Mattsson, K., Flaberg, E., Kati, E., Markasz, L., Sheldon, J. A., Klein, G., Schulz, T. F. & Szekely, L. (2007). HHV-8 encoded LANA-1 alters the higher organization of the cell nucleus. Mol Cancer 6:28.

    Article  PubMed  CAS  Google Scholar 

  • Su, P. F., Lee, T. C., Lin, P. J., Lee, P. H., Jeng, Y. M., Chen, C. H., Liang, J. D., Chiou, L. L., Huang, G. T. & Lee, H. S. (2007). Differential DNA methylation associated with hepatitis B virus infection in hepatocellular carcinoma. Int J Cancer 121, 1257–1264.

    Article  PubMed  CAS  Google Scholar 

  • Swaminathan, S. (2008). Noncoding RNAs produced by oncogenic human herpesviruses. J Cell Physiol 216, 321–326.

    Article  PubMed  CAS  Google Scholar 

  • Szalmas, A. & Konya, J. (2009). Epigenetic alterations in cervical carcinogenesis. Semin Cancer Biol 19, 144–152.

    Article  PubMed  CAS  Google Scholar 

  • Takacs, M., Banati, F., Koroknai, A., Segesdi, J., Salamon, D., Wolf, H., Niller, H. H. & Minarovits, J. (2010). Epigenetic regulation of latent Epstein-Barr virus promoters. Biochim Biophys Acta 1799, 228–235.

    Article  PubMed  CAS  Google Scholar 

  • Takacs, M., Segesdi, J., Banati, F., Koroknai, A., Wolf, H., Niller, H. H. & Minarovits, J. (2009). The importance of epigenetic alterations in the development of Epstein-Barr virus-related lymphomas. Mediterr J Hematol Infect Dis 1, e2009012.

    PubMed  Google Scholar 

  • Takai, N., Kira, N., Ishii, T., Nishida, M., Nasu, K. & Narahara, H. (2011). Novel chemotherapy using histone deacetylase inhibitors in cervical cancer. Asian Pac J Cancer Prev 12, 575–580.

    PubMed  Google Scholar 

  • Tanner, J. E. & Alfieri, C. (2001). The Epstein-Barr virus and post-transplant lymphoproliferative disease: interplay of immunosuppression, EBV, and the immune system in disease pathogenesis. Transpl Infect Dis 3, 60–69.

    Article  PubMed  CAS  Google Scholar 

  • Tempera, I., Klichinsky, M. & Lieberman, P. M. (2011). EBV latency types adopt alternative chromatin conformations. PLoS Pathog 7, e1002180.

    Article  PubMed  CAS  Google Scholar 

  • Tempera, I. & Lieberman, P. M. (2010). Chromatin organization of gammaherpesvirus latent genomes. Biochim Biophys Acta 1799, 236–245.

    Article  PubMed  CAS  Google Scholar 

  • ter Schegget, J., Voves, J., van Strien, A. & van der Noordaa J. (1980). Free viral DNA in BK virus-induced hamster tumor cells. J Virol 35, 331–339.

    PubMed  Google Scholar 

  • Thorley-Lawson, D. A. (2004). EBV and Burkitt’s lymphoma. N Engl J Med 350, 2621.

    Article  CAS  Google Scholar 

  • Timms, J. M., Bell, A., Flavell, J. R., Murray, P. G., Rickinson, A. B., Traverse-Glehen, A., Berger, F. & Delecluse, H. J. (2003). Target cells of Epstein-Barr-virus (EBV)-positive post-transplant lymphoproliferative disease: similarities to EBV-positive Hodgkin’s lymphoma. Lancet 361, 217–223.

    Article  PubMed  Google Scholar 

  • Tischoff, I. & Tannapfel, A. (2008). DNA methylation in hepatocellular carcinoma. World J Gastroenterol 14, 1741–1748.

    Article  PubMed  CAS  Google Scholar 

  • Tobollik, S., Meyer, L., Buettner, M., Klemmer, S., Kempkes, B., Kremmer, E., Niedobitek, G. & Jungnickel, B. (2006). Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth. Blood 108, 3859–3864.

    Article  PubMed  CAS  Google Scholar 

  • Toth, Z., Maglinte, D. T., Lee, S. H., Lee, H. R., Wong, L. Y., Brulois, K. F., Lee, S., Buckley, J. D., Laird, P. W., Marquez, V. E. & Jung, J. U. (2010). Epigenetic analysis of KSHV latent and lytic genomes. PLoS Pathog 6, e1001013.

    Article  PubMed  CAS  Google Scholar 

  • Tsai, C. L., Li, H. P., Lu, Y. J., Hsueh, C., Liang, Y., Chen, C. L., Tsao, S. W., Tse, K. P., Yu, J. S. & Chang, Y. S. (2006). Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling. Cancer Res 66, 11668–11676.

    Article  PubMed  CAS  Google Scholar 

  • Tsai, C. N., Tsai, C. L., Tse, K. P., Chang, H. Y. & Chang, Y. S. (2002). The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases. Proc Natl Acad Sci U S A 99, 10084–10089.

    Article  PubMed  CAS  Google Scholar 

  • Uchida, J., Yasui, T., Takaoka-Shichijo, Y., Muraoka, M., Kulwichit, W., Raab-Traub, N. & Kikutani, H. (1999). Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 286, 300–303.

    Article  PubMed  CAS  Google Scholar 

  • Um, T. H., Kim, H., Oh, B. K., Kim, M. S., Kim, K. S., Jung, G. & Park, Y. N. (2011). Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis. J Hepatol 54, 939–947.

    Article  PubMed  CAS  Google Scholar 

  • Umehara, T., Nakamura, Y., Wakamori, M., Ozato, K., Yokoyama, S. & Padmanabhan, B. (2010). Structural implications for K5/K12-di-acetylated histone H4 recognition by the second bromodomain of BRD2. FEBS Lett 584, 3901–3908.

    Article  PubMed  CAS  Google Scholar 

  • Ushiku, T., Chong, J. M., Uozaki, H., Hino, R., Chang, M. S., Sudo, M., Rani, B. R., Sakuma, K., Nagai, H. & Fukayama, M. (2007). p73 gene promoter methylation in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer 120, 60–66.

    Article  PubMed  CAS  Google Scholar 

  • Ushmorov, A., Leithauser, F., Ritz, O., Barth, T. F., Moller, P. & Wirth, T. (2008). ABF-1 is frequently silenced by promoter methylation in follicular lymphoma, diffuse large B-cell lymphoma and Burkitt’s lymphoma. Leukemia 22, 1942–1944.

    Article  PubMed  CAS  Google Scholar 

  • van den Bosch, C. A. (2004). Is endemic Burkitt’s lymphoma an alliance between three infections and a tumour promoter? Lancet Oncol 5, 738–746.

    Article  PubMed  Google Scholar 

  • Van Keymeulen, A., Mascre, G., Youseff, K. K., Harel, I., Michaux, C., De Geest, N., Szpalski, C., Achouri, Y., Bloch, W., Hassan, B. A. & Blanpain, C. (2009). Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 187, 91–100.

    Article  PubMed  CAS  Google Scholar 

  • Viejo-Borbolla, A., Ottinger, M., Bruning, E., Burger, A., Konig, R., Kati, E., Sheldon, J. A. & Schulz, T. F. (2005). Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi’s Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1. J Virol 79, 13618–13629.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L., Grossman, S. R. & Kieff, E. (2000). Epstein-Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter. Proc Natl Acad Sci U S A 97, 430–435.

    Article  PubMed  CAS  Google Scholar 

  • Wentzensen, N., Sherman, M. E., Schiffman, M. & Wang, S. S. (2009). Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol Oncol 112, 293–299.

    Article  PubMed  CAS  Google Scholar 

  • Wisman, G. B., Nijhuis, E. R., Hoque, M. O., Reesink-Peters, N., Koning, A. J., Volders, H. H., Buikema, H. J., Boezen, H. M., Hollema, H., Schuuring, E., Sidransky, D. & van der Zee, A. G. (2006). Assessment of gene promoter hypermethylation for detection of cervical neoplasia. Int J Cancer 119, 1908–1914.

    Article  PubMed  CAS  Google Scholar 

  • Yanatatsaneejit, P., Mutirangura, A. & Kitkumthorn, N. (2011). Human papillomavirus’s physical state and cyclin A1 promoter methylation in cervical cancer. Int J Gynecol Cancer 21, 902–906.

    Article  PubMed  Google Scholar 

  • Yang, B., Guo, M., Herman, J. G. & Clark, D. P. (2003). Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol 163, 1101–1107.

    Article  PubMed  CAS  Google Scholar 

  • Yasui, D. H., Peddada, S., Bieda, M. C., Vallero, R. O., Hogart, A., Nagarajan, R. P., Thatcher, K. N., Farnham, P. J. & LaSalle, J. M. (2007). Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci U S A 104, 19416–19421.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, B., Laribee, R. N., Klemsz, M. J. & Roman, A. (2004). Human papillomavirus type 16 E7 protein increases acetylation of histone H3 in human foreskin keratinocytes. Virology 329, 189–198.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y. J., Chen, Y., Ahsan, H., Lunn, R. M., Chen, S. Y., Lee, P. H., Chen, C. J. & Santella, R. M. (2005). Silencing of glutathione S-transferase P1 by promoter hypermethylation and its relationship to environmental chemical carcinogens in hepatocellular carcinoma. Cancer Lett 221, 135–143.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, Z., Pan, J., Chu, B., Wong, Y. C., Cheung, A. L. & Tsao, S. W. (1999). Downregulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. Hum Pathol 30, 458–466.

    Article  PubMed  CAS  Google Scholar 

  • Zhong, S., Yeo, W., Tang, M. W., Wong, N., Lai, P. B. & Johnson, P. J. (2003). Intensive hypermethylation of the CpG island of Ras association domain family 1A in hepatitis B virus-associated hepatocellular carcinomas. Clin Cancer Res 9, 3376–3382.

    PubMed  CAS  Google Scholar 

  • Zhou, J., Chau, C. M., Deng, Z., Shiekhattar, R., Spindler, M. P., Schepers, A. & Lieberman, P. M. (2005). Cell cycle regulation of chromatin at an origin of DNA replication. EMBO J 24, 1406–1417.

    Article  PubMed  CAS  Google Scholar 

  • zur Hausen H. (2002). Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2, 342–350.

    Google Scholar 

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  1. Institute for Medical Microbiology and Hygiene at the University of Regensburg, Regensburg, Germany

    Hans Helmut Niller MD

  2. Microbiological Research Group, National Center for Epidemiology, Budapest, Hungary

    Ferenc Banati, Eva Ay & Janos Minarovits MD, MSc

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  1. Microbiological Research Group, National Center for Epidemiology, Piheno u. 1, Budapest, 1529, Hungary

    Janos Minarovits

  2. University of Regensburg, Regensburg, 93053, Germany

    Hans Helmut Niller

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Niller, H.H., Banati, F., Ay, E., Minarovits, J. (2012). Epigenetic Changes in Virus-Associated Neoplasms. In: Minarovits, J., Niller, H. (eds) Patho-Epigenetics of Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3345-3_8

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