title: Frequent epigenetic silencing of the FHIT gene in penile squamous cell carcinomas.
abstract: Methylation of normally unmethylated CpG-rich islands in or near the promoter region has been associated with transcriptional inactivation of tumor-suppressor and tumor-related genes in human cancers. However, so far, only a few studies have searched for DNA methylation in penile carcinoma (PC). On the other hand, human papillomavirus (HPV) has been reported to be associated with the pathogenesis of PC. To elucidate the methylation status of PC and HPV infection, the methylation status of eight genes (DAPK, FHIT, MGMT, p14, p16, RAR-beta, RASSF1A, and RUNX3), the incidences of the HPV status, and the expression of Fhit protein were examined in 25 PCs. The frequencies of methylation were: 28% for DAPK, 92% for FHIT, 20% for MGMT, 4% for p14, 24% for p16, 24% for RAR-beta, 12% for RASSF1A, and 44% for RUNX3. Negative expression of Fhit protein was observed in 22 of the 25 cancers (88%). Among those 22, 20 showed methylation of the FHIT gene. HPV-DNA was detected in three of the 25 cancers (12%). Methylation of FHIT gene was frequently found than HPV infection, therefore methylation of the FHIT gene is suggested to play an important role in the pathogenesis of penile squamous cell carcinoma.
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan. nyanagaw@med.id.yamagata-u.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Osakabe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D064550:Death-Associated Protein Kinases; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000235:genetics; D010412:Penile Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D050677:Core Binding Factor Alpha 3 Subunit; D004273:DNA, Neoplasm; D064550:Death-Associated Protein Kinases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C493729:Runx3 protein, human