title: Clinical significance of hypermethylation status in NSCLC: evaluation of a 30-gene panel in patients with advanced disease.
abstract: BACKGROUND
  DNA methylation is one of major factors in cancer progression. We observed multiple genes involved in cancer-related signaling and focused on patients with advanced non-small cell lung cancer (NSCLC) and evaluated methylation in relation to various clinical parameters.
  
  
  METHODS
  Thirty genes were examined in 121 NSCLC patients using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method. Correlations to gender, smoking status, tumor subtype, disease stage and EGFR/KRAS mutation status were performed by chi-square test.
  
  
  RESULTS
  90% of tumors exhibited methylation of at least one gene. Most frequently methylated were cadherin-13 (CDH13), Ras associated domain-containing protein (RASSF1A), Wilms' tumor protein (WT1), adenomatous polyposis coli protein (APC), paired box protein Pax-5 (PAX5), estrogen receptor (ESR1), an inhibitor of cyclin-dependent kinase p15 (CDKN2B), paired box protein Pax-6 (PAX6), transcription factor GATA-5 (GATA5) and cell adhesion molecule 4 (IGSF4). Overall methylation (any gene) was increased in adenocarcinomas (p=0.0329), unrelated to gender or disease stage. Several genes exhibited variable methylation with gender (CDH13, p<0.001; GATA5, p=0.02; PAX6, p=0.01 and ESR1, p=0.03), smoking (CDH13, p=0.002), or epidermal growth factor receptor (EGFR) mutation status [Von Hippel-Lindau disease tumor supresor (VHL), p=0.001; CDKN2B, p=0.02; CDH13, p=0.02; APC, p=0.04 and ESR1, p=0.04].
  
  
  CONCLUSIONS
  Differences in gene methylation associated with gender, smoking and EGFR mutation suggest potential for prediction in relation to management of tyrosine kinase inhibitor therapy.
authors.affiliation: Department of Pneumology, Faculty Hospital Pilsen, Pilsen, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Pesek
authors.forename: Marta
authors.initials: M
authors.lastname: Kopeckova
authors.forename: Lucie
authors.initials: L
authors.lastname: Benesova
authors.forename: Anna
authors.initials: A
authors.lastname: Meszarosova
authors.forename: Petr
authors.initials: P
authors.lastname: Mukensnabl
authors.forename: Frantisek
authors.initials: F
authors.lastname: Bruha
authors.forename: Marek
authors.initials: M
authors.lastname: Minarik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D066246:ErbB Receptors