title: Genomewide DNA methylation analysis identifies novel methylated genes in non-small-cell lung carcinomas.
abstract: BACKGROUND
  DNA methylation is part of the epigenetic regulatory mechanism present in all normal cells. It is tissue-specific and stably maintained throughout development, but often abnormally changed in cancer. Non-small-cell lung carcinoma (NSCLC) is the most deadly type of cancer, involving different tumor subtypes. This heterogeneity is a challenge for correct diagnosis and patient treatment. The stability and specificity make of DNA methylation a very suitable marker for epigenetic phenotyping of tumors.
  
  
  METHODS
  To identify candidate markers for use in NSCLC diagnosis, we used genomewide DNA methylation maps that we had previously generated by MethylCap and next-generation sequencing and listed the most significant differentially methylated regions (DMRs). The 25 DMRs with highest significance in their methylation scores were selected. The methylation status of these DMRs was investigated in 61 tumors and matching control lung tissues by methylation-specific polymerase chain reaction.
  
  
  RESULTS
  We found 12 novel DMRs that showed significant differences between tumor and control lung tissues. We also identified three novel DMRs for each of the two most common NSCLC subtypes, adenocarcinomas and squamous cell carcinomas. We propose a panel of five DMRs, composed of novel and known markers that exhibit high specificity and sensitivity to distinguish tumors from control lung tissues.
  
  
  CONCLUSIONS
  Novel markers will aid the development of a highly specific epigenetic panel for accurate identification and subtyping of NSCLC tumors.
authors.affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rejane Hughes
authors.initials: RH
authors.lastname: Carvalho
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Vanja
authors.initials: V
authors.lastname: Haberle
authors.forename: Joachim
authors.initials: J
authors.lastname: Aerts
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers