PURPOSE: To investigate the prevalence, distribution, and prognostic role of BRAF mutations in a large cohort of white patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A retrospective series of 1,046 NSCLCs-comprising 739 adenocarcinomas (ADCs) and 307 squamous cell carcinomas (SCCs)-was investigated for BRAF mutations. High-resolution melting analysis followed by sequencing and strip hybridization assay were used. All patients were also analyzed for KRAS and EGFR mutations. RESULTS: BRAF mutations were present in 36 ADCs (4.9%) and one SCC (0.3%; P = .001). Twenty-one of the mutations (56.8%) were V600E, and 16 (43.2%) were non-V600E. V600E mutations were significantly more prevalent in females (16 of 187 patients; 8.6%) than in males (five of 552 patients; 0.9%), as indicated by multivariate logistic regression analysis (hazard ratio [HR], 11.29; P < .001). V600E-mutated tumors showed an aggressive histotype characterized by micropapillary features in 80% of patients and were significantly associated with shorter disease-free and overall survival rates on both univariate (HR, 2.67; P < .001 and HR, 2.97; P < .001, respectively) and multivariate analyses (HR, 2.19; P = .011 and HR, 2.18; P = .014, respectively). All non-V600E mutations were found in smokers (P = .015) and were associated with neither clinicopathologic parameters nor prognosis. BRAF and EGFR were concomitantly mutated in two tumors. CONCLUSION: We report for the first time to our knowledge that V600E and non-V600E BRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations.
PURPOSE: To investigate the prevalence, distribution, and prognostic role of BRAF mutations in a large cohort of white patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A retrospective series of 1,046 NSCLCs-comprising 739 adenocarcinomas (ADCs) and 307 squamous cell carcinomas (SCCs)-was investigated for BRAF mutations. High-resolution melting analysis followed by sequencing and strip hybridization assay were used. All patients were also analyzed for KRAS and EGFR mutations. RESULTS:BRAF mutations were present in 36 ADCs (4.9%) and one SCC (0.3%; P = .001). Twenty-one of the mutations (56.8%) were V600E, and 16 (43.2%) were non-V600E. V600E mutations were significantly more prevalent in females (16 of 187 patients; 8.6%) than in males (five of 552 patients; 0.9%), as indicated by multivariate logistic regression analysis (hazard ratio [HR], 11.29; P < .001). V600E-mutated tumors showed an aggressive histotype characterized by micropapillary features in 80% of patients and were significantly associated with shorter disease-free and overall survival rates on both univariate (HR, 2.67; P < .001 and HR, 2.97; P < .001, respectively) and multivariate analyses (HR, 2.19; P = .011 and HR, 2.18; P = .014, respectively). All non-V600E mutations were found in smokers (P = .015) and were associated with neither clinicopathologic parameters nor prognosis. BRAF and EGFR were concomitantly mutated in two tumors. CONCLUSION: We report for the first time to our knowledge that V600E and non-V600EBRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations.
Authors: Kadoaki Ohashi; Lecia V Sequist; Maria E Arcila; Teresa Moran; Juliann Chmielecki; Ya-Lun Lin; Yumei Pan; Lu Wang; Elisa de Stanchina; Kazuhiko Shien; Keisuke Aoe; Shinichi Toyooka; Katsuyuki Kiura; Lynnette Fernandez-Cuesta; Panos Fidias; James Chih-Hsin Yang; Vincent A Miller; Gregory J Riely; Mark G Kris; Jeffrey A Engelman; Cindy L Vnencak-Jones; Dora Dias-Santagata; Marc Ladanyi; William Pao Journal: Proc Natl Acad Sci U S A Date: 2012-07-06 Impact factor: 11.205
Authors: Alessandro Russo; Ana Rita Lopes; Michael G McCusker; Sandra Gimenez Garrigues; Giuseppina R Ricciardi; Katherine E Arensmeyer; Katherine A Scilla; Ranee Mehra; Christian Rolfo Journal: Curr Oncol Rep Date: 2020-04-16 Impact factor: 5.075
Authors: Luping Lin; Saurabh Asthana; Elton Chan; Sourav Bandyopadhyay; Maria M Martins; Victor Olivas; Jenny Jiacheng Yan; Luu Pham; Mingxue Michelle Wang; Gideon Bollag; David B Solit; Eric A Collisson; Charles M Rudin; Barry S Taylor; Trever G Bivona Journal: Proc Natl Acad Sci U S A Date: 2014-02-03 Impact factor: 11.205
Authors: David M Hyman; Igor Puzanov; Vivek Subbiah; Jason E Faris; Ian Chau; Jean-Yves Blay; Jürgen Wolf; Noopur S Raje; Eli L Diamond; Antoine Hollebecque; Radj Gervais; Maria Elena Elez-Fernandez; Antoine Italiano; Ralf-Dieter Hofheinz; Manuel Hidalgo; Emily Chan; Martin Schuler; Susan Frances Lasserre; Martina Makrutzki; Florin Sirzen; Maria Luisa Veronese; Josep Tabernero; José Baselga Journal: N Engl J Med Date: 2015-08-20 Impact factor: 91.245