title: Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues.
abstract: OBJECTIVE
  The aim of this study is to clarify genome-wide DNA methylation profiles in renal tumors of various histological subtypes.
  
  
  METHODS
  Bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using tissue samples of 17 patients with papillary renal cell carcinomas (RCCs), chromophobe RCCs and oncocytomas, and the results were compared with those from 51 patients with clear cell RCCs.
  
  
  RESULTS
  Unsupervised hierarchical clustering analysis based on DNA methylation status clustered type 1 and type 2 papillary RCCs into different subclasses. Although chromophobe RCCs and oncocytomas were clustered into the same subclass, the DNA methylation status of 21 BAC clones was able to discriminate chromophobe RCCs from oncocytomas. The number of BAC clones showing DNA methylation alteration in non-tumorous renal tissue from patients with chromophobe RCCs and oncocytomas was smaller than that from patients with clear cell RCCs. Biphasic accumulation of DNA methylation alterations was observed in non-tumorous renal tissue from all 68 patients, and patients showing such alterations on more BAC clones had a poorer outcome than patients showing them on fewer BAC clones.
  
  
  CONCLUSIONS
  DNA methylation profiles determining the histological subtypes of renal tumors developing in individual patients and/or patient outcome may be already established in non-tumorous renal tissue at the precancerous stage.
authors.affiliation: Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Arai
authors.forename: Saori
authors.initials: S
authors.lastname: Wakai-Ushijima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Fumie
authors.initials: F
authors.lastname: Hosoda
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Sana
authors.initials: S
authors.lastname: Yokoi
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D018249:Adenoma, Oxyphilic / Q000235:genetics / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D016000:Cluster Analysis; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis