KRAS and BRAF Double Mutations and Functional Classes of BRAF Mutations in Non–small-cell Lung Cancers

Abstract

We read with great interest the study by Myall et al comparing, notably, the clinicopathologic and molecular features of BRAF V600E and BRAF non-V600E mutated non–small-cell lung cancer (NSCLC). 1 Myall N.J. Henry S. Wood D. et al. Natural disease history, outcomes, and co-mutations in a series of patients with BRAF-Mutated non-small-cell lung cancer. Clin Lung Cancer. 2019; 20: e208-e217 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar In their study about 18 patients with BRAF-mutated NSCLC (corresponding to a frequency of 2.7% of NSCLC), the fact that they did not observe any co-occurring KRAS mutations particularly retained our attention. Indeed, some studies have also supported the concept that BRAF and KRAS alterations were mutually exclusive in NSCLC. 2 Marchetti A. Felicioni L. Malatesta S. et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol. 2011; 29: 3574-3579 Crossref PubMed Scopus (417) Google Scholar , 3 Paik P.K. Arcila M.E. Fara M. et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011; 29: 2046-2051 Crossref PubMed Scopus (527) Google Scholar , 4 Villaruz L.C. Socinski M.A. Abberbock S. et al. Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium. Cancer. 2015; 121: 448-456 Crossref PubMed Scopus (85) Google Scholar , 5 Litvak A.M. Paik P.K. Woo K.M. et al. Clinical characteristics and course of 63 patients with BRAF mutant lung cancers. J Thorac Oncol. 2014; 9: 1669-1674 Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar , 6 Auliac J.B. Bayle S. Vergnenegre A. et al. Patients with non-small-cell lung cancer harbouring a BRAF mutation: a multicentre study exploring clinical characteristics, management, and outcomes in a real-life setting: EXPLORE GFPC 02-14. Curr Oncol. 2018; 25: e398-402 Crossref PubMed Scopus (8) Google Scholar Nevertheless, several other studies have reported a considerable number of double BRAF and KRAS mutants (up to about 14% of BRAF-mutated NSCLC). 7 Cardarella S. Ogino A. Nishino M. et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res. 2013; 19: 4532-4540 Crossref PubMed Scopus (257) Google Scholar , 8 Tissot C. Couraud S. Tanguy R. Bringuier P.P. Girard N. Souquet P.J. Clinical characteristics and outcome of patients with lung cancer harboring BRAF mutations. Lung Cancer. 2016; 91: 23-28 Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar , 9 Brustugun O.T. Khattak A.M. Trømborg A.K. et al. BRAF-mutations in non-small cell lung cancer. Lung Cancer. 2014; 84: 36-38 Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar , 10 Dagogo-Jack I. Martinez P. Yeap B.Y. et al. Impact of BRAF mutation class on disease characteristics and clinical outcomes in BRAF-mutant lung cancer. Clin Cancer Res. 2019; 25: 158-165 Crossref PubMed Scopus (55) Google Scholar , 11 Salimian K.J. Fazeli R. Zheng G. Ettinger D. Maleki Z. V600E BRAF versus Non-V600E BRAF mutated lung adenocarcinomas: cytomorphology, histology, coexistence of other driver mutations and patient characteristics. Acta Cytol. 2018; 62: 79-84 Crossref PubMed Scopus (9) Google Scholar , 12 Ding X. Zhang Z. Jiang T. et al. Clinicopathologic characteristics and outcomes of Chinese patients with non-small-cell lung cancer and BRAF mutation. Cancer Med. 2017; 6: 555-562 Crossref PubMed Scopus (30) Google Scholar