Abstract C20: Quantitative determination of EGFR gene aberrant methylation in NSCLC: a comparative analysis in tumor tissue, normal lung tissue, peripheral blood, sputum and bronchial aspirate
Authors: Rocio Lavado-Valenzuela, Enrique Bermejo, Roberto Mongil, Francisco Páez, Carlos Pagés, Miguel Angel Berciano, Ricardo Arrabal, Dolores Bautista, Jose Luis De la Cruz, Cynthia Robles, Manuel Benavides, Manuel Cobo
Journal: Cancer Research (2013)

Abstract Introduction and objective. To evaluate and compare quantitatively aberrant methylation in the promoter area of EGFR gene in patients (p) with in non small cell lung cancer (NSCLC) lung tumor tissue (TT), lung normal tissue (NT), blood (B), bronchial aspirate (BA) and sputum (S). Correlate these methylation patterns with clinical variables. Methods. DNA was extracted from samples of B, S and BA from patients with NSCLC prior to surgery and resected TT and NT. Methylation patterns were analyzed by the bisulfite conversion and subsequent pyrosequencing (QIagen PyroMark System). We analyzed three CpG islands in the promoter region of EGFR gene. Results. 43p were included, median age 66 years (range 46-79), 35 men and 8 women. Histology: 26p adenocarcinoma, 14 squamous and 3 others. 2p had EGFR mutation. Smoking status: 4p never smokers, 21p former smokers, 18p smokers. Significant differences in methylation percentage (%Mth) were observed between TT and S in the following islands: CpG2 (11.8vs7.1, p = 0.008), CpG3 (10vs7.4, p = 0.037) and in overall promoter area (10.6vs7. 6, p = 0.034). The %Mth was higher in women vs men in TT CpG1 island (16.2vs24.9, p = 0.042) and TT CpG2 island (15.8vs26.5, p = 0.013). The %Mth was higher in squamous histology compared to adenocarcinoma in NT CpG2 island (22.6vs14.1, p = 0.017) and S CpG1 island (13.7vs8.2, p = 0.047). However, the %Mth was higher in the overall promoter area of adenocarcinoma respect to squamous histology (19.7vs12.8 TT, p = 0.042). The %Mth was higher in overall promoter area of NT respect Stage I vs II vs III (22.3 vs 13 vs 17.5, p = 0.03). The %Mth was higher in former smokers compared to current smokers and non smokers in NT CpG3 (22.8 vs 13 vs 14.1, p = 0.032). The %Mth in NT CpG3 was higher in never smokers and former smokers &amp;gt; 5 years, respect to current smokers and former smokers &amp;lt;5 years, (23.3 vs 15.8, p = 0.05). Conclusion. EGFR aberrant hypermethylation was higher in tumor tissue respect to sputum, with no correlation with EGFR mutation. The %Mth in normal tissue was higher in never smoker and former smokers &amp;gt; 5 years patients. * This study was funded by the Carlos III Health Institute (PS09/00308), Spain Note: This abstract was not presented at the conference. Citation Format: Rocio Lavado-Valenzuela, Enrique Bermejo, Roberto Mongil, Francisco Páez, Carlos Pagés, Miguel Angel Berciano, Ricardo Arrabal, Dolores Bautista, Jose Luis De la Cruz, Cynthia Robles, Manuel Benavides, Manuel Cobo. Quantitative determination of EGFR gene aberrant methylation in NSCLC: a comparative analysis in tumor tissue, normal lung tissue, peripheral blood, sputum and bronchial aspirate. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C20.