title: Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer.
abstract: BACKGROUND
  Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options.
  
  
  OBJECTIVE
  Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidation is needed to reveal therapeutically actionable targets in ACC.
  
  
  METHODS
  In this study, global DNA methylation levels were assessed by the Infinium HumanMethylation450 BeadChip Array on 18 ACC tumors and 6 normal adrenal tissues. A new, non-linear correlation approach, the discretization method, assessed the relationship between DNA methylation/gene expression across ACC tumors.
  
  
  RESULTS
  This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as silencing of the tumor suppressor MARCKS, previously unreported in ACC.
  
  
  CONCLUSIONS
  DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors.
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Christophe R
authors.initials: CR
authors.lastname: Legendre
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Demeure
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Whitsett
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Gooden
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.|NantOmics, LLC, Phoenix, Arizona, United States of America.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Bussey
authors.affiliation: Department of Genome Medicine and Science, Gachon University School of Medicine, Incheon, 21565, Republic of Korea.|Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, 21565, Republic of Korea.
authors.forename: Sungwon
authors.initials: S
authors.lastname: Jung
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Tembe
authors.initials: T
authors.lastname: Waibhav
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Seungchan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, United States of America.
authors.forename: Bodour
authors.initials: B
authors.lastname: Salhia
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins