A critical role of cis-regulation of expression by methylation in lung adenocarcinoma and intrinsic resistance to EGFR-TKIs were found both in the discovery (79 tumors sampled from patients with advanced lung adenocarcinoma before receiving EGFR-TKI) and in the validation cohort (163 patients with EGFR-activating mutations) of NSCLC patients. The gene discussed is EGFR; the disease is lung adenocarcinoma.