Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI’s Lung Cancer Mutation Consortium (LCMC).

作者：Mark G. Kris, Bruce E. Johnson, D J Kwiatkowski, A. John Iafrate, Ignacio I. Wistuba, S. L. Aronson, Jeffrey A. Engelman, Y. Shyr, F. R. Khuri, C. M. Rudin, Edward B. Garon, William Pao, J. H. Schiller, E. B. Haura, K. Shirai, G. Giaccone, L. D. Berry, K. Kugler, J. D. Minna, P. A. Bunn · 发表于：Journal of Clinical Oncology · 年份：2011 · DOI：10.1200/jco.2011.29.18_suppl.cra7506 · 被引用次数：142 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics

CRA7506 Background: The ability to detect driver mutations like EGFR and EML4-ALK in tumor specimens from patients with lung cancer and administer agents targeting those molecular lesions has revolutionized the management of adenocarcinoma of the lung. The availability of multiplexed assays to detect mutations permits the identification of multiple driver mutations from tumors at diagnosis. The number of molecular lesions and new agents to target them continues to grow. To exploit this, we created the LCMC to determine 10 driver mutations in tumors from 1,000 patients and to give the results to clinicians for care and entry onto targeted therapeutic trials based on these findings. Methods: The 14 member LCMC is prospectively enrolling patients to test tumors from patients with lung adenocarcinoma in CLIA laboratories for KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, MEK1, and NRAS using standard multiplexed assays and fluorescence in situ hybridization (FISH) for ALK rearrangements and MET amplifications. All are stage IIIB/IV, PS 0-2, have available tissue, and signed consent. Results: 830 patients have been registered with 50 enrolling monthly. We detected a driver mutation in 60% (252/422, 95% CI 55 to 65%) of tumors thus far. Mutations found: KRAS 107 (25%, 95% CI 21 to 30%), EGFR 98 (23%, 95% CI 19 to 27%), ALK rearrangements 14 (6%, 95% CI 4 to11%), BRAF 12 (3%, 95% CI 1 to 5%), PIK3CA 11 (3%, 95% CI 1 to 5%), MET amplifications 4 (2%, 95% CI 0.5 to 5%), HER2 3, (1%, 95% CI 0.1...