title: CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer.
abstract: Urothelial carcinomas (TCC) constitute the vast majority of bladder cancers in most of the world. On the other hand, squamous cell bladder carcinoma, a rare subtype in the Western world, is a common subtype in areas with endemic Schistosoma infection. Although schistosomal infection has been reported to influence DNA methylation, the pattern and extent of CpG island hypermethylation in squamous cell carcinomas remain unknown. In this study, we used methylation-specific PCR to characterize 12 cancer-related genes in 41 bladder cancer samples from Egypt (31 squamous cell carcinomas (SCC), 21 of them associated with Schistosoma and 10 TCC, five of which were Schistosoma-associated). The genes analyzed included E-cadherin, DAP-Kinase, O6MGMT, p14, p15, p16, FHIT, APC, RASSF1A, GSTP1, RARbeta and p73. Methylation of at least one gene was detected in all squamous cell tumors except two, and 45% of samples had at least three methylated genes. The average methylation index was 0.24, corresponding to three of the 12 analyzed genes. Schistosoma-associated tumors had more genes methylated than non-Schistosoma tumors (average MI: 0.29 vs 0.14) (P = 0.027). Although the extent of methylation in TCC (average MI: 0.16) was lower than in squamous cell carcinomas (SCC), the overall profile of methylation was similar, with Schistosoma-associated cases having a higher methylation index. Our results suggest that schistosomal involvement associates with a greater degree of epigenetic changes in the bladder epithelium.
authors.affiliation: King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Marina I
authors.initials: MI
authors.lastname: Gutiérrez
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Siraj
authors.forename: Hussein
authors.initials: H
authors.lastname: Khaled
authors.forename: Natalie
authors.initials: N
authors.lastname: Koon
authors.forename: Wa'el
authors.initials: W
authors.lastname: El-Rifai
authors.forename: Kishor
authors.initials: K
authors.lastname: Bhatia
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D064550:Death-Associated Protein Kinases; D016147:Genes, Tumor Suppressor; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012553:Schistosomiasis haematobia / Q000150:complications*; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D025601:Adenomatous Polyposis Coli Protein; D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D064550:Death-Associated Protein Kinases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D018168:Receptors, Retinoic Acid; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C493966:CDKN2B protein, human; C411762:RASSF1 protein, human; C000606460:TP73 protein, human; C082925:retinoic acid receptor beta; C496556:GSTP1 protein, human