title: GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma.
abstract: Transcriptional inactivation and CpG island (CGI) methylation of GATA transcription factor family members GATA3 and GATA5 have been reported for a few types of human cancer. Whether high-density CGI methylation of GATA3 or GATA5 is associated with the clinical course of patients with renal cell cancer (RCC) has not been clarified. Quantitative methylation-specific PCR assays were carried out to analyze 25 tumor cell lines including 6 RCC lines and 119 RCC and 87 adjacent normal tissues for the presence of densely methylated sequences. Methylation values were statistically compared with clinicopathological and recurrence-free survival (RFS) data for patients. Comparison of GATA3 and GATA5 methylation in different tumor cell lines revealed a marker-specific methylation characteristic with high and frequent signals for both methylation marks in RCC lines. GATA3 and GATA5 CGI relative methylation levels were found to be strongly associated with the state of metastasis (P=0.003 and P<0.001, respectively) and advanced disease (P=0.024 and P<0.001, respectively). Moreover, an independent decrease in RFS in Cox proportional hazard analysis was found for tumors exhibiting high GATA5 methylation (P<0.001, hazard ratio, 19.3; 95% confidence interval, 4.58-81.6). Epigenetic alterations in GATA family members may be associated with aggressive tumor phenotypes in RCC, and in the case of GATA5, may serve as a new independent molecular marker for aggressiveness and disease progression.
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Peters
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Gebauer
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Dubrowinskaja
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Faranaz
authors.initials: F
authors.lastname: Atschekzei
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Mario W
authors.initials: MW
authors.lastname: Kramer
authors.affiliation: Department of Urology, Eberhard-Karls University, D-72076 Tuebingen, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Hennenlotter
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Hossein
authors.initials: H
authors.lastname: Tezval
authors.affiliation: Department of Pathology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abbas
authors.affiliation: Department of Biometry, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Scherer
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.affiliation: Department of Urology, Eberhard-Karls University, D-72076 Tuebingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Serth
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D050992:GATA5 Transcription Factor / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human