Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations

作者: Michael Fara , Camelia S. Sima , Vincent A. Miller , Mark G. Kris , Marc Ladanyi

DOI: 10.1200/JCO.2010.33.1280

关键词:

摘要: Purpose BRAF mutations occur in non–small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. Patients and Methods We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. Results Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). Conclusion BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.

参考文章(35)
Keith T. Flaherty, Grant McArthur, BRAF, a target in melanoma: implications for solid tumor drug development. Cancer. ,vol. 116, pp. 4902- 4913 ,(2010) , 10.1002/CNCR.25261
R. Kefford, H. Arkenau, M. P. Brown, M. Millward, J. R. Infante, G. V. Long, D. Ouellet, M. Curtis, P. F. Lebowitz, G. S. Falchook, Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. Journal of Clinical Oncology. ,vol. 28, pp. 8503- 8503 ,(2010) , 10.1200/JCO.2010.28.15_SUPPL.8503
Marcia S Brose, Patricia Volpe, Michael Feldman, Madhu Kumar, Irum Rishi, Renee Gerrero, Eugene Einhorn, Meenhard Herlyn, John Minna, Andrew Nicholson, Jack A Roth, Steven M Albelda, Helen Davies, Charles Cox, Graham Brignell, Philip Stephens, P Andrew Futreal, Richard Wooster, Michael R Stratton, Barbara L Weber, None, BRAF and RAS mutations in human lung cancer and melanoma Cancer Research. ,vol. 62, pp. 6997- 7000 ,(2002)
Hong Yang, Brian Higgins, Kenneth Kolinsky, Kathryn Packman, Zenaida Go, Raman Iyer, Stanley Kolis, Sylvia Zhao, Richard Lee, Joseph F. Grippo, Kathleen Schostack, Mary Ellen Simcox, David Heimbrook, Gideon Bollag, Fei Su, RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models Cancer Research. ,vol. 70, pp. 5518- 5527 ,(2010) , 10.1158/0008-5472.CAN-10-0646
Qiulu Pan, William Pao, Marc Ladanyi, Rapid Polymerase Chain Reaction-Based Detection of Epidermal Growth Factor Receptor Gene Mutations in Lung Adenocarcinomas The Journal of Molecular Diagnostics. ,vol. 7, pp. 396- 403 ,(2005) , 10.1016/S1525-1578(10)60569-7
Christian Jurinke, Paul Oeth, Dirk van den Boom, MALDI-TOF mass spectrometry: a versatile tool for high-performance DNA analysis. Molecular Biotechnology. ,vol. 26, pp. 147- 163 ,(2004) , 10.1385/MB:26:2:147
Gregory J. Riely, Mark G. Kris, Daniel Rosenbaum, Jenifer Marks, Allan Li, Dhananjay A. Chitale, Khedoudja Nafa, Elyn R. Riedel, Meier Hsu, William Pao, Vincent A. Miller, Marc Ladanyi, Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clinical Cancer Research. ,vol. 14, pp. 5731- 5734 ,(2008) , 10.1158/1078-0432.CCR-08-0646
Poulikos I. Poulikakos, Chao Zhang, Gideon Bollag, Kevan M. Shokat, Neal Rosen, RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF Nature. ,vol. 464, pp. 427- 430 ,(2010) , 10.1038/NATURE08902
Claudia Wellbrock, Adam Hurlstone, BRAF as therapeutic target in melanoma Biochemical Pharmacology. ,vol. 80, pp. 561- 567 ,(2010) , 10.1016/J.BCP.2010.03.019