DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection
<p>Abstract</p> <p>Background</p> <p>Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.</p> <p>Methods<...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-08-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/8/238 |
| _version_ | 1818832764145762304 |
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| author | Goldberg José Oliveira Maria Camargo João Favaro Francine P Negraes Priscilla D Rainho Cláudia A Salvadori Daisy MF |
| author_facet | Goldberg José Oliveira Maria Camargo João Favaro Francine P Negraes Priscilla D Rainho Cláudia A Salvadori Daisy MF |
| author_sort | Goldberg José |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.</p> <p>Methods</p> <p>A set of 4 genes, including <it>CDH1 </it>(E-cadherin), <it>SFN </it>(stratifin), <it>RARB </it>(retinoic acid receptor, beta) and <it>RASSF1A </it>(Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters.</p> <p>Results</p> <p><it>CDH1 </it>and <it>SFN </it>genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between <it>RARB </it>and <it>RASSF1A </it>methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for <it>RARB </it>methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for <it>RASSF1A </it>gene, respectively, in relation to the control group.</p> <p>Conclusion</p> <p>Indistinct DNA hypermethylation of <it>CDH1 </it>and <it>SFN </it>genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, <it>RARB </it>and <it>RASSF1A </it>gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of differentially methylated genes in this neoplasia in order to maximize the diagnostic coverage of epigenetic markers, especially in studies aiming at early recurrence detection.</p> |
| first_indexed | 2024-12-19T02:08:12Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-19T02:08:12Z |
| publishDate | 2008-08-01 |
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| series | BMC Cancer |
| spelling | doaj.art-ac52e61a3f09499b98ff9f25418cf5582022-12-21T20:40:53ZengBMCBMC Cancer1471-24072008-08-018123810.1186/1471-2407-8-238DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detectionGoldberg JoséOliveira MariaCamargo JoãoFavaro Francine PNegraes Priscilla DRainho Cláudia ASalvadori Daisy MF<p>Abstract</p> <p>Background</p> <p>Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.</p> <p>Methods</p> <p>A set of 4 genes, including <it>CDH1 </it>(E-cadherin), <it>SFN </it>(stratifin), <it>RARB </it>(retinoic acid receptor, beta) and <it>RASSF1A </it>(Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters.</p> <p>Results</p> <p><it>CDH1 </it>and <it>SFN </it>genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between <it>RARB </it>and <it>RASSF1A </it>methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for <it>RARB </it>methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for <it>RASSF1A </it>gene, respectively, in relation to the control group.</p> <p>Conclusion</p> <p>Indistinct DNA hypermethylation of <it>CDH1 </it>and <it>SFN </it>genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, <it>RARB </it>and <it>RASSF1A </it>gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of differentially methylated genes in this neoplasia in order to maximize the diagnostic coverage of epigenetic markers, especially in studies aiming at early recurrence detection.</p>http://www.biomedcentral.com/1471-2407/8/238 |
| spellingShingle | Goldberg José Oliveira Maria Camargo João Favaro Francine P Negraes Priscilla D Rainho Cláudia A Salvadori Daisy MF DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection BMC Cancer |
| title | DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection |
| title_full | DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection |
| title_fullStr | DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection |
| title_full_unstemmed | DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection |
| title_short | DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection |
| title_sort | dna methylation patterns in bladder cancer and washing cell sediments a perspective for tumor recurrence detection |
| url | http://www.biomedcentral.com/1471-2407/8/238 |
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