Dataset Information


Identifying functional CpG island methylation markers in clear cell renal cell cancer cell lines

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is the most common adult renal cancer. Although the molecular characteristics of ccRCC are currently being studied, the biologically and clinically relevant ccRCC methylome remains to be elucidated. To explore the RCC hypermethylome we employed massive sequencing of methyl-binding protein enriched DNA and validated the biological relevance of the identified hypermethylated sites by pharmacological inhibition of DNA methylation. We identified four candidate tumor suppressor genes (GREM1, LAD1, NEFH, and NEURL) of which promoter CpG island hypermethylation was strongly predictive for ccRCC survival in two independent series (n=150 and n=185) of ccRCC primary samples. The four markers combined are strongly associated with risk for cancer-related death in the test series (HR 3.64, 95% CI 1.02-13.01) as well as, independently of other clinicopathological characteristics, in the validation series (HR 7.54, 95% CI 2.68-21.19) using Cox proportional hazard models. According to Harrell’s C statistics and the Akaike Information Criterion (AIC) the four marker panel provides the best predictive capacity with the best fit of the model as assessed for the tested markers. These results provide novel insights into the ccRCC hypermethylome and identify a strong methylation marker panel to potentially guide personalized ccRCC patient management. Preliminary to implementation of this marker panel into clinical practice, enrollment of these patients in a Phase-III trial to study adjuvant treatment efficacy is essential. 4 independant clear cell renal cancer cell lines were used before and after treatment with the DNA methylation inhibitor AZA or the HAZA inhibitor TSA.

ORGANISM(S): Homo sapiens  

SUBMITTER: Tim De Meyer   Stephen B Baylin  Manon van Engeland  Wim Van Criekinge  Iris Vlodrop  Leander Van Neste 

PROVIDER: E-GEOD-33916 | ArrayExpress | 2013-11-22



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