title: DNA methylation profiling identifies global methylation differences and markers of adrenocortical tumors.
abstract: BACKGROUND
  It is not known whether there are any DNA methylation alterations in adrenocortical tumors.
  
  
  OBJECTIVE
  The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors.
  
  
  METHODS
  Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated analysis of genome-wide methylation and mRNA expression in benign vs. malignant adrenocortical tissue samples was also performed.
  
  
  RESULTS
  Methylation profiling revealed the following: 1) that methylation patterns were distinctly different and could distinguish normal, benign, primary malignant, and metastatic tissue samples; 2) that malignant samples have global hypomethylation; and 3) that the methylation of CpG regions are different in benign adrenocortical tumors by functional status. Normal compared with benign samples had the least amount of methylation differences, whereas normal compared with primary and metastatic adrenocortical carcinoma samples had the greatest variability in methylation (adjusted P ≤ 0.01). Of 215 down-regulated genes (≥2-fold, adjusted P ≤ 0.05) in malignant primary adrenocortical tumor samples, 52 of these genes were also hypermethylated.
  
  
  CONCLUSIONS
  Malignant adrenocortical tumors are globally hypomethylated as compared with normal and benign tumors. Methylation profile differences may accurately distinguish between primary benign and malignant adrenocortical tumors. Several differentially methylated sites are associated with genes known to be dysregulated in malignant adrenocortical tumors.
authors.affiliation: Endocrine Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Nesrin S
authors.initials: NS
authors.lastname: Rechache
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.forename: Holly S
authors.initials: HS
authors.lastname: Stevenson
authors.forename: J Keith
authors.initials: JK
authors.lastname: Killian
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Edelman
authors.forename: Maria
authors.initials: M
authors.lastname: Merino
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000302:Adrenal Cortex / Q000502:physiology*; D000306:Adrenal Cortex Neoplasms / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger