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Identification of Novel Epigenetic Markers for Clear Cell Renal Cell Carcinoma

2008; Lippincott Williams & Wilkins; Volume: 180; Issue: 3 Linguagem: Inglês

10.1016/j.juro.2008.04.137

1527-3792

Gul S. Dalgin, Michele Drever, Tara Williams, Thomas C. King, Charles DeLisi, Louis S. Liou,

Renal and related cancers

No AccessJournal of UrologyInvestigative Urology1 Sep 2008Identification of Novel Epigenetic Markers for Clear Cell Renal Cell Carcinomais companion ofvon Hippel-Lindau Gene Status and Response to Vascular Endothelial Growth Factor Targeted Therapy for Metastatic Clear Cell Renal Cell CarcinomaA Phase II Trial of Gemcitabine Plus Capecitabine for Metastatic Renal Cell Cancer Previously Treated With Immunotherapy and Targeted AgentsRisk Score and Metastasectomy Independently Impact Prognosis of Patients With Recurrent Renal Cell Carcinoma Gul S. Dalgin, Michele Drever, Tara Williams, Thomas King, Charles DeLisi, and Louis S. Liou Gul S. DalginGul S. Dalgin Molecular and Cell Biology and Biochemistry Program, Boston University, Boston, Massachusetts , Michele DreverMichele Drever College of Liberal Arts, Boston University, Boston, Massachusetts , Tara WilliamsTara Williams Department of Pathology, Boston University School of Medicine, Boston, Massachusetts , Thomas KingThomas King Department of Pathology, Boston University School of Medicine, Boston, Massachusetts , Charles DeLisiCharles DeLisi Biomedical Engineering, Boston University, Boston, Massachusetts Bioinformatics and Systems Biology, Boston University, Boston, Massachusetts , and Louis S. LiouLouis S. Liou Department of Pathology, Boston University School of Medicine, Boston, Massachusetts Cambridge Health Alliance, Department of Urology, Harvard Medical School, Boston, Massachusetts View All Author Informationhttps://doi.org/10.1016/j.juro.2008.04.137AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We identified significantly hypermethylated genes in clear cell renal cell carcinoma. Materials and Methods: We previously identified a set of under expressed genes in renal cell carcinoma tissue through transcriptional profiling and a robust computational screen. We selected 19 of these genes for hypermethylation analysis using a rigorous search for the best candidate regions, considering CpG islands and transcription factor binding sites. The genes were analyzed for hypermethylation in the DNA of 38 matched clear cell renal cell carcinoma and normal samples using matrix assisted laser desorption ionization time-of-flight mass spectrometry. The significance of hypermethylation was assessed using 3 statistical tests. We validated the down-regulation of significantly hypermethylated genes at the RNA and protein levels in a separate set of patients using reverse transcriptase-polymerase chain reaction, immunohistochemistry and Western blots. Results: We found 7 significantly hypermethylated regions from 6 down-regulated genes, including SFRP1, which was previously shown to be hypermethylated in renal cell carcinoma and other cancer types. Conclusions: To our knowledge we report for the first time that another 5 genes (SCNN1B, SYT6, DACH1, and the tumor suppressors TFAP2A and MT1G) are hypermethylated in renal cell carcinoma. Robust computational screens and the high throughput methylation assay resulted in an enriched set of novel genes that are epigenetically altered in clear cell renal cell carcinoma. Overall the detection of hypermethylation in these highly down-regulated genes suggests that assaying for their methylation using cells from urine or blood could provide the basis for a viable diagnostic test. References 1 : Cancer statistics. CA Cancer J Clin2007; 57: 43. Google Scholar 2 : Promoter hypermethylation of tumor suppressor genes in urine from kidney cancer patients. Cancer Res2003; 63: 8695. Google Scholar 3 : Quantitative detection of promoter hypermethylation of multiple genes in the tumor, urine, and serum DNA of patients with renal cancer. Cancer Res2004; 64: 5723. Google Scholar 4 : Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet2000; 24: 132. Google Scholar 5 : The power and the promise of DNA methylation markers. Nat Rev Cancer2003; 3: 253. 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Google Scholar © 2008 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology17 Jul 2008von Hippel-Lindau Gene Status and Response to Vascular Endothelial Growth Factor Targeted Therapy for Metastatic Clear Cell Renal Cell CarcinomaJournal of Urology17 Jul 2008A Phase II Trial of Gemcitabine Plus Capecitabine for Metastatic Renal Cell Cancer Previously Treated With Immunotherapy and Targeted AgentsJournal of Urology17 Jul 2008Risk Score and Metastasectomy Independently Impact Prognosis of Patients With Recurrent Renal Cell Carcinoma Volume 180Issue 3September 2008Page: 1126-1130 Advertisement Copyright & Permissions© 2008 by American Urological AssociationKeywordscarcinomamicroarray analysiskidneybiologicalrenal cellmethylationtumor markersAcknowledgmentsMathias Ehrich assisted with methylation experiments and data structure technical support.MetricsAuthor Information Gul S. Dalgin Molecular and Cell Biology and Biochemistry Program, Boston University, Boston, Massachusetts More articles by this author Michele Drever College of Liberal Arts, Boston University, Boston, Massachusetts More articles by this author Tara Williams Department of Pathology, Boston University School of Medicine, Boston, Massachusetts More articles by this author Thomas King Department of Pathology, Boston University School of Medicine, Boston, Massachusetts More articles by this author Charles DeLisi Biomedical Engineering, Boston University, Boston, Massachusetts Bioinformatics and Systems Biology, Boston University, Boston, Massachusetts More articles by this author Louis S. Liou Department of Pathology, Boston University School of Medicine, Boston, Massachusetts Cambridge Health Alliance, Department of Urology, Harvard Medical School, Boston, Massachusetts Financial interest and/or other relationship with Abbot Molecular and Quest Diagnostic. 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