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| Status |
Public on Nov 22, 2013 |
| Title |
Identifying functional CpG island methylation markers in clear cell renal cell cancer cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Van Neste L, Vlodrop I, De Meyer T, van Engeland M, Baylin SB, Van Criekinge W |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 23, 2011 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Leander Van Neste |
| Organization name |
Ghent University
|
| Department |
Molecular Biotechnology
|
| Lab |
Bioinformatics and Computational Genomics
|
| Street address |
Coupure Links 653
|
| City |
Ghent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (8)
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| GSM838695 |
Effect of AZA treatment on gene expression in SKRC59 |
| GSM838696 |
Effect of TSA treatment on gene expression in SKRC59 |
| GSM838697 |
Effect of AZA treatment on gene expression in SKRC52 |
| GSM838698 |
Effect of TSA treatment on gene expression in SKRC52 |
| GSM838699 |
Effect of AZA treatment on gene expression in SKRC1 |
| GSM838700 |
Effect of TSA treatment on gene expression in SKRC1 |
| GSM838701 |
Effect of AZA treatment on gene expression in SKRC10 |
| GSM838702 |
Effect of TSA treatment on gene expression in SKRC10 |
|
| Relations |
| BioProject |
PRJNA148235 |
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