title: Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer death in men and women in the United States and Western Europe. Over 160,000 Americans die of this disease every year. The five-year survival rate is 15% - significantly lower than that of other major cancers. Early detection is a key factor in increasing lung cancer patient survival. DNA hypermethylation is recognized as an important mechanism for tumor suppressor gene inactivation in cancer and could yield powerful biomarkers for early detection of lung cancer. Here we focused on developing DNA methylation markers for squamous cell carcinoma of the lung. Using the sensitive, high-throughput DNA methylation analysis technique MethyLight, we examined the methylation profile of 42 loci in a collection of 45 squamous cell lung cancer samples and adjacent non-tumor lung tissues from the same patients.
  
  
  RESULTS
  We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25, TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection, this eight-locus panel showed 95.6% sensitivity and specificity.
  
  
  CONCLUSIONS
  We have identified 22 DNA methylation markers for squamous cell lung cancer, several of which have not previously been reported to be methylated in any type of human cancer. The top eight markers show great promise as a sensitive and specific DNA methylation marker panel for squamous cell lung cancer.
authors.affiliation: Department of Surgery, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089-9176, USA. anglim@usc.edu
authors.forename: Paul P
authors.initials: PP
authors.lastname: Anglim
authors.forename: Janice S
authors.initials: JS
authors.lastname: Galler
authors.forename: Michael N
authors.initials: MN
authors.lastname: Koss
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hagen
authors.forename: Sally
authors.initials: S
authors.lastname: Turla
authors.forename: Mihaela
authors.initials: M
authors.lastname: Campan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisenberger
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: Ite A
authors.initials: IA
authors.lastname: Laird-Offringa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor