title: Alterations in chromatin accessibility and DNA methylation in clear cell renal cell carcinoma.
abstract: Recent studies have demonstrated that in clear cell renal cell carcinoma (ccRCC) several chromatin remodeling enzymes are genetically inactivated. Although, growing evidence in cancer models has demonstrated the importance of epigenetic changes, currently only changes in DNA methylation can be accurately determined from clinical samples. To address this limitation, we have applied formaldehyde-assisted isolation of regulatory elements (FAIREs) combined with next-generation sequencing (FAIRE-seq) to identify specific changes in chromatin accessibility in clinical samples of ccRCC. We modified the FAIRE procedure to allow us to examine chromatin accessibility for small samples of solid tumors. Our FAIRE results were compared with DNA-methylation analysis and show how chromatin accessibility decreases at many sites where DNA-methylation remains unchanged. In addition, our FAIRE-seq analysis allowed us to identify regulatory elements associated with both normal and tumor tissue. We have identified decreases in chromatin accessibility at key ccRCC-linked genes, including PBRM1, SETD2 and MLL2. Overall, our results demonstrate the power of examining multiple aspects of the epigenome.
authors.affiliation: 1] Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY, USA [2] Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Buck
authors.affiliation: CanSys Program, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Raaijmakers
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ramakrishnan
authors.affiliation: Biostatistics Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Valiyaparambil
authors.affiliation: Biostatistics Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1] Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY, USA [2] Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Nowak
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pili
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D057890:Epigenomics / Q000379:methods*; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D050436:Regulatory Elements, Transcriptional; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human