Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/69848
標題: Clustered Genomic Alterations in Chromosome 7p Dictate Outcomes and Targeted Treatment Responses of Lung Adenocarcinoma With EGFR-Activating Mutations
作者: Yuan, S.S.
Yu, S.L.
Chen, H.Y.
Hsu, Y.C.
Su, K.Y.
Chen, H.W.
Chen, C.Y.
Yu, C.J.
Shih, J.Y.
Chang, Y.L.
Cheng, C.L.
Hsu, C.P.
Hsia, J.Y.
Lin, C.Y.
Wu, G.N.
Liu, C.H.
Wang, C.D.
Yang, K.C.
Chen, Y.W.
Lai, Y.L.
Hsu, C.C.
Lin, T.C.
Yang
關鍵字: receptor gene-mutations;molecular-origins;gefitinib therapy;phase-ii;cancer;sensitivity;erlotinib;expression;survival;tumors
Project: Journal of Clinical Oncology
期刊/報告no:: Journal of Clinical Oncology, Volume 29, Issue 25, Page(s) 3435-3442.
摘要: 
Purpose 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. J Clin Oncol 29:3435-3442. (C) 2011 by American Society of Clinical Oncology
URI: http://hdl.handle.net/11455/69848
ISSN: 0732-183X
DOI: 10.1200/jco.2011.35.3979
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