{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:11:13Z","timestamp":1792192273235,"version":"4.4.0"},"reference-count":119,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T00:00:00Z","timestamp":1369267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations in specific genes in a limited number of cases. This review aims to provide an overview of the current knowledge of the epigenetic alterations in PeCa and the promising results in this field. The identification of epigenetically altered genes in PeCa is an important step in understanding the mechanisms involved in this unexplored disease.<\/jats:p>","DOI":"10.3390\/ijms140610791","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T12:56:11Z","timestamp":1369313771000},"page":"10791-10808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Epigenetic Mechanisms in Penile Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Hellen","family":"Kuasne","sequence":"first","affiliation":[{"name":"Department of General Biology, Londrina State University, Londrina, PR 86055-900, Brazil"},{"name":"International Research and Teaching Center, CIPE, AC Camargo Cancer Center, S\u00e3o Paulo,  SP 01508-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Marchi","sequence":"additional","affiliation":[{"name":"Inter-institutional Grad Program on Bioinformatics, Institute of Mathematics and Statistics,  USP\u2014S\u00e3o Paulo University, S\u00e3o Paulo, SP 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rogatto","sequence":"additional","affiliation":[{"name":"International Research and Teaching Center, CIPE, AC Camargo Cancer Center, S\u00e3o Paulo,  SP 01508-010, Brazil"},{"name":"Department of Urology, Faculty of Medicine, UNESP, Botucatu, SP 18618-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilce","family":"De Syllos C\u00f3lus","sequence":"additional","affiliation":[{"name":"Department of General Biology, Londrina State University, Londrina, PR 86055-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,23]]},"reference":[{"key":"ref_1","unstructured":"Parkin, D., Whelan, S., Ferlay, J., Teppo, L., and Thomas, D (2002). Cancer Incidence in Five Continents, IARC Scientific Publications."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.urolonc.2006.08.029","article-title":"Incidence trends in primary malignant penile cancer","volume":"25","author":"Maldonado","year":"2007","journal-title":"Urol. Oncol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S1470-2045(04)01427-5","article-title":"Penile carcinoma: A challenge for the developing world","volume":"5","author":"Misra","year":"2004","journal-title":"Lancet Oncol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eururo.2004.03.007","article-title":"Eau guidelines on penile cancer","volume":"46","author":"Solsona","year":"2004","journal-title":"Eur. Urol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1590\/S1677-55382008000500007","article-title":"Epidemiologic study on penile cancer in Brazil","volume":"34","author":"Favorito","year":"2008","journal-title":"Int. Braz. J. Urol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/ijc.21009","article-title":"Penile cancer: Importance of circumcision, human papillomavirus and smoking in in situ and invasive disease","volume":"116","author":"Daling","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/jso.20980","article-title":"Surgical treatment of invasive squamous cell carcinoma of the penis: Brazilian national cancer institute long-term experience","volume":"97","author":"Ornellas","year":"2008","journal-title":"J. Surg. Oncol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1100\/tsw.2011.24","article-title":"Penile carcinoma: Risk factors and molecular alterations","volume":"11","author":"Calmon","year":"2011","journal-title":"ScientificWorldJournal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.1016\/j.urology.2010.04.008","article-title":"Prognostic factors in penile cancer","volume":"76","author":"Ficarra","year":"2010","journal-title":"Urology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0022-5347(01)65471-5","article-title":"Prognostic factors in carcinoma of the penis: Multivariate analysis of 145 patients treated with amputation and lymphadenectomy","volume":"156","author":"Lopes","year":"1996","journal-title":"J. Urol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.cbpa.2010.06.174","article-title":"Targeting epigenetic enzymes for drug discovery","volume":"14","author":"Copeland","year":"2010","journal-title":"Curr. Opin. Chem. Biol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.molonc.2012.09.004","article-title":"Trials with \u201cepigenetic\u201d drugs: An update","volume":"6","author":"Nebbioso","year":"2012","journal-title":"Mol. Oncol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/00365590050509913","article-title":"Etiology of squamous cell carcinoma of the penis","volume":"205","author":"Dillner","year":"2000","journal-title":"Scand. J. Urol. Nephrol. Suppl"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1001\/archpedi.1980.02130170034012","article-title":"Circumcision and the risk of cancer of the penis. A life-table analysis","volume":"134","author":"Kochen","year":"1980","journal-title":"Am. J. Dis. Child"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1464-410X.1995.tb07352.x","article-title":"The role of tobacco in penile carcinoma","volume":"75","author":"Harish","year":"1995","journal-title":"Br. J. Urol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1136\/jcp.2008.063149","article-title":"Human papillomavirus prevalence and type distribution in penile carcinoma","volume":"62","author":"Bruni","year":"2009","journal-title":"J. Clin. Pathol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1023\/A:1011266405062","article-title":"Risk factors for penile cancer: Results of a population-based case-control study in los angeles county (united states)","volume":"12","author":"Tsen","year":"2001","journal-title":"Cancer Causes Control"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1158\/1055-9965.EPI-08-0456","article-title":"Risk factors for squamous cell carcinoma of the penis\u2014Population-based case-control study in Denmark","volume":"17","author":"Madsen","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E36","DOI":"10.1542\/peds.105.3.e36","article-title":"The highly protective effect of newborn circumcision against invasive penile cancer","volume":"105","author":"Schoen","year":"2000","journal-title":"Pediatrics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00430-003-0181-2","article-title":"Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts","volume":"193","author":"Gross","year":"2004","journal-title":"Med. Microbiol. Immunol"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nrc798","article-title":"Papillomaviruses and cancer: From basic studies to clinical application","volume":"2","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0002-9440(10)62506-0","article-title":"Detection and typing of human papillomavirus dna in penile carcinoma: Evidence for multiple independent pathways of penile carcinogenesis","volume":"159","author":"Rubin","year":"2001","journal-title":"Am. J. Pathol"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1053\/j.semdp.2011.09.001","article-title":"The role of human papillomavirus infection in the pathogenesis of penile squamous cell carcinomas","volume":"29","author":"Chaux","year":"2012","journal-title":"Semin. Diagn. Pathol"},{"key":"ref_24","first-page":"177","article-title":"High prevalence of human papillomavirus 16 in penile carcinoma","volume":"22","author":"Pascual","year":"2007","journal-title":"Histol. Histopathol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10552-008-9276-9","article-title":"Systematic review of human papillomavirus prevalence in invasive penile cancer","volume":"20","author":"Backes","year":"2009","journal-title":"Cancer Causes Control"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1158\/1055-9965.EPI-06-0603","article-title":"Alleviating the burden of cancer: A perspective on advances, challenges, and future directions","volume":"15","author":"Schottenfeld","year":"2006","journal-title":"Cancer Epidemiol. Biomarkers Prev"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1590\/S0100-879X2006000200003","article-title":"Infection with human papillomaviruses of sexual partners of women having cervical intraepithelial neoplasia","volume":"39","author":"Rombaldi","year":"2006","journal-title":"Braz. J. Med. Biol. Res"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/cncr.23764","article-title":"Hpv prophylactic vaccines and the potential prevention of noncervical cancers in both men and women","volume":"113","author":"Gillison","year":"2008","journal-title":"Cancer"},{"key":"ref_29","first-page":"48","article-title":"Infection and cervical neoplasia: Facts and fiction","volume":"2","author":"Smith","year":"2009","journal-title":"Int. J. Clin. Exp. Pathol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0046-8177(00)80245-2","article-title":"Epstein-barr virus (ebv) genes expression in cervical intraepithelial neoplasia and invasive cervical cancer: A comparative study with human papillomavirus (hpv) infection","volume":"31","author":"Sasagawa","year":"2000","journal-title":"Hum. Pathol"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1590\/S0074-02762012000100003","article-title":"Prevalence of human papillomavirus and epstein-barr virus dna in penile cancer cases from brazil","volume":"107","author":"Afonso","year":"2012","journal-title":"Mem. Inst. Oswaldo. Cruz"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1046\/j.1464-410X.2002.02962.x","article-title":"Common skin disorders of the penis","volume":"90","author":"Buechner","year":"2002","journal-title":"BJU Int"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0094-0143(21)00853-3","article-title":"Premalignant lesions and nonsquamous malignancy of the penis and carcinoma of the scrotum","volume":"19","author":"Schellhammer","year":"1992","journal-title":"Urol. Clin. N. Am"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1046\/j.1523-1747.2000.00069.x","article-title":"Erythroplasia of queyrat: Coinfection with cutaneous carcinogenic human papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ","volume":"115","author":"Wieland","year":"2000","journal-title":"J. Invest. Dermatol"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1097\/01.grf.0000179635.64663.3d","article-title":"An overview of lichen sclerosus","volume":"48","author":"Val","year":"2005","journal-title":"Clin. Obstet. Gynecol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1046\/j.1365-2230.2003.01211.x","article-title":"Lichen sclerosus","volume":"28","author":"Tasker","year":"2003","journal-title":"Clin. Exp. Dermatol"},{"key":"ref_37","unstructured":"Sufrin, G., and Huber, R (1991). Benign and Malignant Lesions of the Penis, J.Y. Gillenwater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.critrevonc.2004.09.006","article-title":"Cancer of the penis","volume":"53","author":"Mosconi","year":"2005","journal-title":"Crit. Rev. Oncol. Hematol"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.urology.2010.02.038","article-title":"Developments in the pathology of penile squamous cell carcinomas","volume":"76","author":"Chaux","year":"2010","journal-title":"Urology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.eururo.2010.01.039","article-title":"Eau penile cancer guidelines 2009","volume":"57","author":"Pizzocaro","year":"2010","journal-title":"Eur. Urol"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1177\/106689690401200408","article-title":"Epithelial lesions associated with invasive penile squamous cell carcinoma: A pathologic study of 288 cases","volume":"12","author":"Cubilla","year":"2004","journal-title":"Int. J. Surg. Pathol"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/00000478-199308000-00001","article-title":"Pathologic features of epidermoid carcinoma of the penis. A prospective study of 66 cases","volume":"17","author":"Cubilla","year":"1993","journal-title":"Am. J. Surg. Pathol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0094-0143(21)00386-4","article-title":"Histopathology of malignant lesions of the penis","volume":"19","author":"Lucia","year":"1992","journal-title":"Urol. Clin. N. Am"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/bjs.1800530108","article-title":"The treatment of carcinoma of the penis","volume":"53","author":"Jackson","year":"1966","journal-title":"Br. J. Surg"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sobin, L., and Wittekind, C (2002). TNM Classification of Malignant Tumours, Wiley-Liss. [6th ed.].","DOI":"10.1002\/0471463752"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1097\/01.ju.0000154565.37397.4d","article-title":"Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases","volume":"173","author":"Kroon","year":"2005","journal-title":"J. Urol"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/j.1464-410X.1993.tb16304.x","article-title":"Morbidity following groin dissection for penile carcinoma","volume":"72","author":"Ravi","year":"1993","journal-title":"Br. J. Urol"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1590\/S1677-55382012000200020","article-title":"Video-assisted left inguinal lymphadenectomy for penile cancer","volume":"38","author":"Britto","year":"2012","journal-title":"Int. Braz. J. Urol"},{"key":"ref_49","first-page":"6395","article-title":"Functional, oncologic, and technical outcomes after endoscopic groin dissection for penile carcinoma","volume":"19","author":"Canter","year":"2012","journal-title":"Can. J. Urol"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1016\/S0022-5347(06)00313-2","article-title":"Nomogram predictive of cancer specific survival in patients undergoing partial or total amputation for squamous cell carcinoma of the penis","volume":"175","author":"Kattan","year":"2006","journal-title":"J. Urol"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0022-5347(05)01003-7","article-title":"Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis","volume":"175","author":"Ficarra","year":"2006","journal-title":"J. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1093\/jnci\/87.22.1705","article-title":"Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma","volume":"87","author":"Gregoire","year":"1995","journal-title":"J. Natl. Cancer Inst"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/jnci\/88.19.1361","article-title":"Human papillomavirus type 18: Association with poor prognosis in early stage cervical cancer","volume":"88","author":"Burger","year":"1996","journal-title":"J. Natl. Cancer Inst"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/1097-0142(20010615)91:12<2315::AID-CNCR1263>3.0.CO;2-C","article-title":"Human papillomavirus as a prognostic factor in carcinoma of the penis: Analysis of 82 patients treated with amputation and bilateral lymphadenectomy","volume":"91","author":"Bezerra","year":"2001","journal-title":"Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1464-410X.2010.09770.x","article-title":"Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large swedish cohort of men with penile carcinoma","volume":"108","author":"Kirrander","year":"2011","journal-title":"BJU Int"},{"key":"ref_56","first-page":"817","article-title":"Correlation of cd82 and htert expressions and hpv infection with penile cancer","volume":"17","author":"Zhai","year":"2011","journal-title":"Zhonghua Nan Ke Xue"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/ijc.21961","article-title":"Presence of high-risk human papillomavirus dna in penile carcinoma predicts favorable outcome in survival","volume":"119","author":"Lont","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2217\/epi.11.64","article-title":"New concepts of old epigenetic phenomena and their implications for selecting specific cell populations for epigenomic research","volume":"3","author":"Herceg","year":"2011","journal-title":"Epigenomics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrg1748","article-title":"The epigenetic progenitor origin of human cancer","volume":"7","author":"Feinberg","year":"2006","journal-title":"Nat. Rev. Genet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.cell.2007.01.029","article-title":"The epigenomics of cancer","volume":"128","author":"Jones","year":"2007","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature05919","article-title":"Phenotypic plasticity and the epigenetics of human disease","volume":"447","author":"Feinberg","year":"2007","journal-title":"Nature"},{"key":"ref_62","first-page":"620","article-title":"Regulators of gene expression as biomarkers for prostate cancer","volume":"2","author":"Willard","year":"2012","journal-title":"Am. J. Cancer Res"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.molonc.2010.04.002","article-title":"The epigenetics of breast cancer","volume":"4","author":"Jovanovic","year":"2010","journal-title":"Mol. Oncol"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.gde.2012.02.008","article-title":"Cancer epigenomics: Beyond genomics","volume":"22","author":"Sandoval","year":"2012","journal-title":"Curr. Opin. Genet. Dev"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1093\/hmg\/9.16.2395","article-title":"The DNA methyltransferases of mammals","volume":"9","author":"Bestor","year":"2000","journal-title":"Hum. Mol. Genet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1073\/pnas.052410099","article-title":"Comprehensive analysis of CPG islands in human chromosomes 21 and 22","volume":"99","author":"Takai","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrg2341","article-title":"DNA methylation landscapes: Provocative insights from epigenomics","volume":"9","author":"Suzuki","year":"2008","journal-title":"Nat. Rev. Genet"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/bioinformatics\/bth059","article-title":"An evaluation of new criteria for CPG islands in the human genome as gene markers","volume":"20","author":"Wang","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8462","DOI":"10.1158\/0008-5472.CAN-06-0293","article-title":"Chromosomal instability correlates with genome-wide dna demethylation in human primary colorectal cancers","volume":"66","author":"Rodriguez","year":"2006","journal-title":"Cancer Res"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1023\/A:1025103319328","article-title":"DNA methylation analysis techniques","volume":"4","author":"Dahl","year":"2003","journal-title":"Biogerontology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9821","DOI":"10.1073\/pnas.93.18.9821","article-title":"Methylation-specific PCR: A novel PCR assay for methylation status of CPG islands","volume":"93","author":"Herman","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E32","DOI":"10.1093\/nar\/28.8.e32","article-title":"Methylight: A high-throughput assay to measure DNA methylation","volume":"28","author":"Eads","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1093\/nar\/25.12.2532","article-title":"Cobra: A sensitive and quantitative DNA methylation assay","volume":"25","author":"Xiong","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1093\/nar\/25.12.2529","article-title":"Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (ms-snupe)","volume":"25","author":"Gonzalgo","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1093\/nar\/gkm013","article-title":"Methylation-sensitive high resolution melting (ms-hrm): A new approach for sensitive and high-throughput assessment of methylation","volume":"35","author":"Wojdacz","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1038\/nprot.2007.314","article-title":"DNA methylation analysis by pyrosequencing","volume":"2","author":"Tost","year":"2007","journal-title":"Nat. Protoc"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-1-59745-522-0_5","article-title":"Methylated DNA immunoprecipitation (medip)","volume":"507","author":"Mohn","year":"2009","journal-title":"Methods Mol. Biol"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1101\/gr.7301508","article-title":"Comprehensive high-throughput arrays for relative methylation (charm)","volume":"18","author":"Irizarry","year":"2008","journal-title":"Genome Res"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/nar\/gkp992","article-title":"Mbd-isolated genome sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome","volume":"38","author":"Serre","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref_81","first-page":"45","article-title":"Using luma: A luminometric-based assay for global DNA-methylation","volume":"1","author":"Karimi","year":"2006","journal-title":"Epigenetics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-59745-522-0_7","article-title":"The help assay","volume":"507","author":"Oda","year":"2009","journal-title":"Methods Mol. Biol"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/978-1-62703-269-8_11","article-title":"Enrichment of methylated DNA by methyl-CPG immunoprecipitation","volume":"971","author":"Sonnet","year":"2013","journal-title":"Methods Mol. Biol"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.bbagen.2009.02.001","article-title":"Hunting for the 5th base: Techniques for analyzing DNA methylation","volume":"1790","author":"Ammerpohl","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4161\/epi.7.1.18647","article-title":"Clinical and public health research using methylated dna immunoprecipitation (medip): A comparison of commercially available kits to examine differential DNA methylation across the genome","volume":"7","author":"Noordhuis","year":"2012","journal-title":"Epigenetics"},{"key":"ref_86","first-page":"2246","article-title":"Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progression-free survival in patients and identifies candidate epigenetic markers","volume":"8","author":"Wei","year":"2002","journal-title":"Clin. Cancer Res"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1158\/1078-0432.CCR-10-3431","article-title":"Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma","volume":"17","author":"Vincent","year":"2011","journal-title":"Clin. Cancer Res"},{"key":"ref_88","first-page":"545","article-title":"DNA demethylation is directly related to tumour progression: Evidence in normal, pre-malignant and malignant cells from uterine cervix samples","volume":"10","author":"Musolino","year":"2003","journal-title":"Oncol. Rep"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e9749","DOI":"10.1371\/journal.pone.0009749","article-title":"Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors","volume":"5","author":"Lambert","year":"2010","journal-title":"PLoS One"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/38444","article-title":"Crystal structure of the nucleosome core particle at 2.8 a resolution","volume":"389","author":"Luger","year":"1997","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1063127","article-title":"Translating the histone code","volume":"293","author":"Jenuwein","year":"2001","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/bcr2925","article-title":"Epigenetics in breast cancer: What\u2019s new?","volume":"13","author":"Huang","year":"2011","journal-title":"Breast Cancer Res"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1002\/jcb.20604","article-title":"Translating the histone code into leukemia","volume":"96","author":"Linggi","year":"2005","journal-title":"J. Cell Biochem"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrg2843","article-title":"The widespread regulation of microrna biogenesis, function and decay","volume":"11","author":"Krol","year":"2010","journal-title":"Nat. Rev. Genet"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/onc.2011.354","article-title":"DNA methylation-associated silencing of tumor-suppressor micrornas in cancer","volume":"31","author":"Esteller","year":"2012","journal-title":"Oncogene"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7390","DOI":"10.1158\/0008-5472.CAN-06-0800","article-title":"Microrna-cancer connection: The beginning of a new tale","volume":"66","author":"Calin","year":"2006","journal-title":"Cancer Res"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1101\/gad.1444406","article-title":"Extensive post-transcriptional regulation of micrornas and its implications for cancer","volume":"20","author":"Thomson","year":"2006","journal-title":"Genes Dev"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/ng.2007.30","article-title":"Widespread microrna repression by MYC contributes to tumorigenesis","volume":"40","author":"Chang","year":"2008","journal-title":"Nat. Genet"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1158\/1078-0432.CCR-11-2010","article-title":"Molecular pathways: Micrornas as cancer therapeutics","volume":"18","author":"Melo","year":"2012","journal-title":"Clin. Cancer Res"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.3748\/wjg.v18.i22.2745","article-title":"Interrelationship between microsatellite instability and microrna in gastrointestinal cancer","volume":"18","author":"Yamamoto","year":"2012","journal-title":"World J. Gastroenterol"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1586\/erm.12.21","article-title":"Great potential of mirnas as predictive and prognostic markers for cancer","volume":"12","author":"Cho","year":"2012","journal-title":"Expert Rev. Mol. Diagn"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nbt.1678","article-title":"Epigenetic modifications as therapeutic targets","volume":"28","author":"Kelly","year":"2010","journal-title":"Nat. Biotechnol"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e39917","DOI":"10.1371\/journal.pone.0039917","article-title":"Hemd: An integrated tool of human epigenetic enzymes and chemical modulators for therapeutics","volume":"7","author":"Huang","year":"2012","journal-title":"PLoS One"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/path.1394","article-title":"Evidence for at least three alternative mechanisms targeting the p16ink4a\/cyclin d\/rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus","volume":"201","author":"Ferreux","year":"2003","journal-title":"J. Pathol"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1365-2133.2006.07604.x","article-title":"Inactivation of the cdkn2a and the p53 tumour suppressor genes in external genital carcinomas and their precursors","volume":"156","author":"Soufir","year":"2007","journal-title":"Br. J. Dermatol"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1002\/ijc.23707","article-title":"Human papillomavirus-16 and -18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation","volume":"123","author":"Kalantari","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1464-410X.2008.07603.x","article-title":"Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma","volume":"102","author":"Guerrero","year":"2008","journal-title":"BJU Int"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1440-1827.2008.02259.x","article-title":"Detection of HPV-DNA, p53 alterations, and methylation in penile squamous cell carcinoma in japanese men","volume":"58","author":"Yanagawa","year":"2008","journal-title":"Pathol. Int"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00428-008-0597-6","article-title":"Frequent epigenetic silencing of the FHIT gene in penile squamous cell carcinomas","volume":"452","author":"Yanagawa","year":"2008","journal-title":"Virchows. Arch"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.juro.2012.08.221","article-title":"Histone methylation defines an epigenetic entity in penile squamous cell carcinoma","volume":"189","author":"Rogenhofer","year":"2012","journal-title":"J. Urol"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00428-010-1007-4","article-title":"Alterations in the tumor suppressor gene p16(ink4a) are associated with aggressive behavior of penile carcinomas","volume":"458","author":"Poetsch","year":"2011","journal-title":"Virchows. Arch"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-1-4615-5371-7_9","article-title":"Contribution of the dual coding capacity of the p16ink4a\/mts1\/cdkn2 locus to human malignancies","volume":"3","author":"Larsen","year":"1997","journal-title":"Prog. Cell Cycle Res"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cell.2006.10.003","article-title":"The regulation of ink4\/arf in cancer and aging","volume":"127","author":"Kim","year":"2006","journal-title":"Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/16476","article-title":"The oncogene and polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus","volume":"397","author":"Jacobs","year":"1999","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1111\/cas.12009","article-title":"Prognostic value of human papillomavirus and squamous cell carcinoma antigen in head and neck squamous cell carcinoma","volume":"103","author":"Deng","year":"2012","journal-title":"Cancer Sci"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"891","DOI":"10.7314\/APJCP.2012.13.3.891","article-title":"Human papillomavirus infection and prognostic predictors in patients with oropharyngeal squamous cell carcinoma","volume":"13","author":"Huang","year":"2012","journal-title":"Asian Pac. J. Cancer Prev"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1172\/JCI12749","article-title":"Thrombospondins as matricellular modulators of cell function","volume":"107","author":"Bornstein","year":"2001","journal-title":"J. Clin. Invest"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/annonc\/mds635","article-title":"Penile cancer: Current therapy and future directions","volume":"24","author":"Sonpavde","year":"2013","journal-title":"Ann. 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