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BRAF MUTATIONS IN NON-SMALL CELL LUNG CANCER – A RARE TARGETABLE DRIVER MUTATION

Introduction: BRAF is a proto-oncogene encoding a serine/threonine protein kinase which is a downstream effector of RAS and transduces signals through the MAPK pathway to promote cell proliferation and survival. Although BRAF mutations are commonly seen in melanoma and papillary thyroid cancer, other cancers may also harbour BRAF mutations. We aimed to investigate the prevalence and clinicopathological features of BRAF mutations in non-small cell lung cancer (NSCLC). Methods: Tumours were genotyped using the Sequenom MassARRAY platform with the OncoCarta panel v1.0. Results: 224 cases of NSCLC were tested and four (1.8%) were found to have BRAF mutations. All four cases (3 males and 1 female, age range 70–76, all smokers) were adenocarcinomas that were wild type for EGFR and KRAS. V600E was identified in two cases and the others were K601N and L597Q mutations. Discussion: Other studies have reported BRAF mutation prevalence between 2% and 5% in NSCLC. The spectrum of mutations is also similar with 50% of mutations being non-V600E (compared to predominant V600E mutations in melanoma). Novel RAF inhibitors are being used to treat melanoma and may potentially be therapeutic to the small subset of NSCLC patients with BRAF mutations. However, the significance of the different mutation spectrum remains unknown.