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Alterations in chromatin accessibility and DNA methylation in clear cell renal cell carcinoma

Oncogene volume 33, pages 4961–4965 (2014)Cite this article

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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.

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Acknowledgements

This research was supported in part by the National Cancer Institute at the National Institutes of Health (P30CA016056; to RP), a grant from the RPCI -Alliance Foundation (to RP) and a donation from the, The Bruce Cuvelier Family Trust (to RP).

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Authors and Affiliations

  1. Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY, USA

    M J Buck, S Valiyaparambil & N J Nowak

  2. Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA

    M J Buck & N J Nowak

  3. CanSys Program, Roswell Park Cancer Institute, Buffalo, NY, USA

    L M Raaijmakers

  4. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    S Ramakrishnan & R Pili

  5. Biostatistics Roswell Park Cancer Institute, Buffalo, NY, USA

    D Wang & S Liu

Authors
  1. M J Buck
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  2. L M Raaijmakers
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  3. S Ramakrishnan
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  4. D Wang
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  5. S Valiyaparambil
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  6. S Liu
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  7. N J Nowak
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Correspondence to M J Buck, N J Nowak or R Pili.

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The authors declare no conflict of interest.

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Buck, M., Raaijmakers, L., Ramakrishnan, S. et al. Alterations in chromatin accessibility and DNA methylation in clear cell renal cell carcinoma. Oncogene 33, 4961–4965 (2014). https://doi.org/10.1038/onc.2013.455

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