Molecular biology and treatment strategies for non-V600 BRAF-mutant NSCLC
| Autor: | Rebecca Nagy, Kimberly C. Banks, Richard B. Lanman, Victoria M. Raymond, Bianca E. Amador, Sai-Hong Ignatius Ou, Trever G. Bivona, Young Kwang Chae, Viola W. Zhu, Patrick Kwok Shing Ng, Jeffrey Crawford, Jeffrey M. Clarke, Marcelo V. Negrao, John V. Heymach, Emily Roarty, Caroline E. McCoach, David R. Gandara |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 37:3102-3102 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 3102 Background: BRAF alterations (alts) account for ~4% of non-small cell lung cancers (NSCLC) with 50% being non-V600 alts. Because these alts are functionally heterogeneous and have a poorly characterized genomic landscape, determining appropriate treatment strategies is a challenge. Methods: The Guardant360 clinical database was queried for NSCLC patients (pts) with BRAF alts. Alts were categorized by clonality, type and class (1 and 2: BRAF monomer and dimer signaling; 3: requires co-occurring upstream RAS-mediated signaling). Functionality and drug screen assays were performed in Ba/F3 cells. Pts with non-V600 mutations were analyzed for sensitivity to MEK +/- BRAF inhibitors (M+Bi). Results: 306 unique BRAF alts were identified and the majority were observed once (233/306; 76%). Amplifications (806/1663; 48.5%) and missense alts (795/1663; 47.8%) were the most common occurrences. Missense alts were predominantly clonal (58%), and of known functionality (428/795; 54%). All class 1-2 alts were activating in Ba/F3 cells, while class 3 alts were found to have variable functionality (activating: 4/9). Functionality was correlated with clonality as demonstrated by class 1-3 alts having higher clonality compared to variants of unknown significance (VUS) (1: 56%; 2: 54%; 3: 45%; VUS: 38%; P |
| Databáze: | OpenAIRE |
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