title: DNA methylation profiling distinguishes histological subtypes of renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) accounts for around 3% of cancers in the UK, and both incidence and mortality are increasing with the aging population. RCC can be divided into several subtypes: conventional RCC (the most common, comprising 75% of all cases), papillary RCC (15%) and chromophobe RCC (5%). Renal oncocytoma is a benign tumor and accounts for 5% of RCC. Cancer and epigenetics are closely associated, with DNA hypermethylation being widely accepted as a feature of many cancers. In this study the DNA methylation profiles of chromophobe RCC and renal oncocytomas were investigated by utilizing the Infinium HumanMethylation450 BeadChips. Cancer-specific hypermethylation was identified in 9.4% and 5.2% of loci in chromophobe RCC and renal oncocytoma samples, respectively, while the majority of the genome was hypomethylated. Thirty (hypermethylated) and 41 (hypomethylated) genes were identified as differentially methylated between chromophobe RCC and renal oncocytomas (p < 0.05). Pathway analysis identified some of the differentially hypermethylated genes to be involved in Wnt (EN2), MAPK (CACNG7) and TGFβ (AMH) signaling, Hippo pathway (NPHP4), and cell death and apoptosis (SPG20, NKX6-2, PAX3 and BAG2). In addition, we analyzed ccRCC and papillary RCC data available from The Cancer Genome Atlas portal to identify differentially methylated loci in chromophobe RCC and renal oncocytoma in relation to the other histological subtypes, providing insight into the pathology of RCC subtypes and classification of renal tumors.
authors: Centre for Rare Diseases and Personalised Medicine, Department of Medical & Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK.
authors: Amy A
authors: AA
authors: Slater
authors: Majed
authors: M
authors: Alokail
authors: Dean
authors: D
authors: Gentle
authors: Masahiro
authors: M
authors: Yao
authors: Gyula
authors: G
authors: Kovacs
authors: Eamonn R
authors: ER
authors: Maher
authors: Farida
authors: F
authors: Latif
mesh_terms: D018249:Adenoma, Oxyphilic / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D007680:Kidney Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D016212:Transforming Growth Factor beta
keywords: chromophobe renal cell carcinoma; hypermethylation; hypomethylation; renal cell carcinoma; renal oncocytoma