title: Genome-wide methylation patterns in papillary thyroid cancer are distinct based on histological subtype and tumor genotype.
abstract: BACKGROUND
  Aberrant DNA methylation is known to be a major factor in oncogenesis and cancer progression, but effects of methylation in papillary thyroid cancer (PTC) are not well defined.
  
  
  OBJECTIVE
  The objective of the study was to identify altered methylation patterns, which may be associated with PTC disease behavior.
  
  
  METHODS
  This study was a genome-wide methylation analysis of PTC.
  
  
  METHODS
  The study was conducted at the National Institutes of Health Clinical Center.
  
  
  METHODS
  PTC tissue from 51 patients were analyzed and compared with normal thyroid tissue from seven patients.
  
  
  METHODS
  CpG methylation status was assessed using advanced genome-wide methylation bead chips.
  
  
  METHODS
  Altered methylation patterns in PTC were analyzed by stage, recurrence, histological subtype of tumor, and tumor genotype.
  
  
  RESULTS
  PTC is globally hypomethylated compared with normal thyroid with 2837 differentially methylated CpG sites. The follicular variant of PTC demonstrated less differential methylation with only 569 differentially methylated CpG sites. Tumors with mutations in BRAF, RET/PTC, and RAS demonstrated a 3.6-fold increase in the number of differentially methylated sites compared with wild-type tumors. The differentially methylated genes were associated with oncological pathways including cellular movement, growth, and proliferation.
  
  
  CONCLUSIONS
  PTC is epigenetically distinct from the follicular variant of PTC and by gene mutation status (BRAF, RET/PTC, and RAS).
authors.affiliation: Endocrine Oncology Branch (R.J.E., M.B., D.P., N.N., M.H., L.Z., E.K.), Genetics Branch (Y.W., H.S.S., S.D., D.C.E., P.S.M.), and Laboratory of Pathology (M.J.M.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; and Perelman School of Medicine (R.J.E.), University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.forename: Holly S
authors.initials: HS
authors.lastname: Stevenson
authors.forename: Myriem
authors.initials: M
authors.lastname: Boufraqech
authors.forename: Dhaval
authors.initials: D
authors.lastname: Patel
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.forename: Sean
authors.initials: S
authors.lastname: Davis
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Edelman
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Mei
authors.initials: M
authors.lastname: He
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051096:Proto-Oncogene Proteins c-ret; D048493:Proto-Oncogene Proteins B-raf