DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection


Autoria(s): Negraes, Priscilla D.; Favaro, Francine P.; Camargo, João Lauro Viana de; Oliveira, Maria Luiza Cotrim Sartor de; Goldberg, José; Rainho, Claudia A.; Salvadori, Daisy Maria Favero
Contribuinte(s)

Universidade Estadual Paulista (UNESP)

Data(s)

20/05/2014

20/05/2014

14/08/2008

Resumo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Processo FAPESP: 03/11730-8

Processo FAPESP: 04/00108-7

Background: 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.Methods: A set of 4 genes, including CDH1 (E-cadherin), SFN (stratifin), RARB (retinoic acid receptor, beta) and RASSF1A (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.Results: CDH1 and SFN 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 RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for RASSF1A gene, respectively, in relation to the control group.Conclusion: Indistinct DNA hypermethylation of CDH1 and SFN genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, RARB and RASSF1A 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.

Formato

12

Identificador

http://dx.doi.org/10.1186/1471-2407-8-238

Bmc Cancer. London: Biomed Central Ltd., v. 8, p. 12, 2008.

1471-2407

http://hdl.handle.net/11449/12929

10.1186/1471-2407-8-238

WOS:000259072700002

WOS000259072700002.pdf

Idioma(s)

eng

Publicador

Biomed Central Ltd.

Relação

BMC Cancer

Direitos

openAccess

Tipo

info:eu-repo/semantics/article