title: Role of DNA methylation in renal cell carcinoma.
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.
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. knirajshenoy@gmail.com.
authors.forename: Niraj
authors.initials: N
authors.lastname: Shenoy
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. vnishanth@gmail.com.
authors.forename: Nishanth
authors.initials: N
authors.lastname: Vallumsetla
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. yiyu.zou@einstein.yu.edu.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. nahungaleas@yahoo.com.
authors.forename: Jose Nahun
authors.initials: JN
authors.lastname: Galeas
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. makardhwaj.shrivastava@gmail.com.
authors.forename: Makardhwaj
authors.initials: M
authors.lastname: Shrivastava
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. caroline.hu@einstein.yu.edu.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hu
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. ksusztak@mail.med.upenn.edu.
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. amit.verma@einstein.yu.edu.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D006801:Humans; D008875:Middle Aged