Yuan S.SUNG-LIANG YUChen H.-Y.Hsu Y.-C.KANG-YI SUHUEI-WEN CHENChen C.-Y.CHONG-JEN YUJIN-YUAN SHIHYIH-LEONG CHANGCheng C.-L.Hsu C.-P.Hsia J.-Y.Lin C.-Y.Wu G.Liu C.-H.Wang C.-D.Yang K.-C.Chen Y.-W.Lai Y.-L.Hsu C.-C.Lin T.-C.Yang T.-Y.Chen K.-C.Hsu K.-H.Chen J.J.W.Chang G.-C.Li K.-C.PAN-CHYR YANG2020-08-132020-08-1320110732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-80052691368&doi=10.1200%2fJCO.2011.35.3979&partnerID=40&md5=d5606d4e89f8ea32d677fdabc428f7fahttps://scholars.lib.ntu.edu.tw/handle/123456789/512677Purpose: Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proven more effective for patients with lung adenocarcinoma with EGFR-activating mutation rather than wild type, the former group still includes approximately 30% nonresponders. The molecular basis of this substantial response heterogeneity is unknown. Our purpose was to seek molecular aberrations contributing to disease progression at the genome-wide level and identify the prognostic signature unique to patients with EGFR-activating mutation. Patients and Methods: We first investigated the molecular differences between tumors with EGFR-activating mutation and wild-type tumors by conducting high-density array comparative genomic hybridization on a collection of 138 adenocarcinoma tissues. We then used an independent group of 114 patients to validate the clinical relevance of copy-number alterations (CNAs) in predicting overall and disease-free survival. Finally, focusing on 23 patients with EGFR mutation receiving EGFR-TKI treatment, we investigated the association between CNAs and response to EGFR-TKIs. Results: We identified chromosome regions with differential CNAs between tumors with EGFR-activating mutation and wild-type tumors and found the aberration sites to cluster highly on chromosome 7p. A cluster of six representative chromosome 7p genes predicted overall and disease-free survival for patients with EGFR-activating mutation but not for those with wild type. Importantly, simultaneous presence of more genes with increased CNAs in this cluster correlated with less favorable response to EGFR-TKIs in patients with EGFR-activating mutation. Conclusion: Our results shed light on why responses to EGFR-TKIs are heterogeneous among patients with EGFR-activating mutation. They may lead to better patient management in this population. ? 2011 by American Society of Clinical Oncology.[SDGs]SDG3epidermal growth factor receptor; erlotinib; gefitinib; adult; article; cancer tissue; chromosome 7p; chromosome aberration; chromosome mutation; comparative genomic hybridization; controlled study; copy number variation; disease course; disease free survival; female; gene; gene cluster; genetic association; human; human cell; human tissue; lung adenocarcinoma; major clinical study; male; overall survival; priority journal; treatment outcome; treatment response; wild type; Adenocarcinoma; Aged; Carcinoma, Non-Small-Cell Lung; Chromosome Aberrations; Chromosomes, Human, Pair 7; Comparative Genomic Hybridization; DNA Mutational Analysis; DNA, Neoplasm; Female; Follow-Up Studies; Gene Dosage; Genome, Human; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Polymerase Chain Reaction; Prognosis; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor; Survival Ratejournal article10.1200/JCO.2011.35.3979218106912-s2.0-80052691368