Role of DNA methylation in renal cell carcinoma

Niraj Shenoy, Nishanth Vallumsetla, Yiyu Zou, Jose Nahun Galeas, Makardhwaj Shrivastava, Caroline Hu, Katalin Susztak, Amit Verma

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Alterations in DNA methylation are seen in cancers and have also been examined in clear cell renal cell carcinoma (ccRCC). Numerous tumor suppressor genes have been reported to be partially or completely silenced due to hypermethylation of their promoters in single-locus studies, and the use of hypomethylating agents has been shown to restore the expression of many of these genes in vitro. In particular, members of the Wnt and TGF-beta pathways, pro-apoptotic genes such as APAF-1 and negative cell-cycle regulators such as KILLIN have been shown to be epigenetically silenced in numerous studies in ccRCC. Recently, TCGA analysis of a large cohort of ccRCC samples demonstrated that aberrant hypermethylation correlated with the stage and grade in kidney cancer. Our genome-wide studies also revealed aberrant widespread hypermethylation that affected regulatory regions of the kidney genome in ccRCC. We also observed that aberrant enhancer hypermethylation was predictive of adverse prognosis in ccRCC. Recent discovery of mutations affecting epigenetic regulators reinforces the importance of these changes in the pathophysiology of ccRCC and points to the potential of epigenetic modulators in the treatment of this malignancy.

Original languageEnglish (US)
Article number88
JournalJournal of Hematology and Oncology
Volume8
Issue number1
DOIs
StatePublished - Jul 22 2015

Fingerprint

DNA Methylation
Renal Cell Carcinoma
Epigenomics
Genome
Kidney Neoplasms
Nucleic Acid Regulatory Sequences
Tumor Suppressor Genes
Transforming Growth Factor beta
Neoplasms
Cell Cycle
Kidney
Gene Expression
Mutation
Genes

Keywords

  • DNA methylation
  • Epigenetics
  • Kidney cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology

Cite this

Role of DNA methylation in renal cell carcinoma. / Shenoy, Niraj; Vallumsetla, Nishanth; Zou, Yiyu; Galeas, Jose Nahun; Shrivastava, Makardhwaj; Hu, Caroline; Susztak, Katalin; Verma, Amit.

In: Journal of Hematology and Oncology, Vol. 8, No. 1, 88, 22.07.2015.

Research output: Contribution to journalArticle

Shenoy, Niraj ; Vallumsetla, Nishanth ; Zou, Yiyu ; Galeas, Jose Nahun ; Shrivastava, Makardhwaj ; Hu, Caroline ; Susztak, Katalin ; Verma, Amit. / Role of DNA methylation in renal cell carcinoma. In: Journal of Hematology and Oncology. 2015 ; Vol. 8, No. 1.
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