Although >90% of BRAF mutations in melanoma involve codon 599 (57 of 60), 8 of 9 BRAF mutations reported to date in NSCLC are non-V599 (89%; P < 10(-7)), strongly suggesting that BRAF mutations in NSCLC are qualitatively different from those in melanoma; thus, there may be therapeutic differences between lung cancer and melanoma in response to RAF inhibitors.
To determine whether loss of wild-type KRAS is involved in the development of human lung cancer, we investigated the mutations of KRAS, NRAS and BRAF in 154 primary non-small cell lung cancers (NSCLCs) as well as 10 NSCLC cell lines that have been shown to have KRAS mutations.
We analyzed the mutational status of exons 9 and 20 and gene copy number of PIK3CA using 86 non-small cell lung cancer (NSCLC) cell lines, 43 small cell lung cancer (SCLC) cell lines, 3 extrapulmonary small cell cancer (ExPuSC) cell lines, and 691 resected NSCLC tumors and studied the relationship between PIK3CA alterations and mutational status of epidermal growth factor receptor (EGFR) signaling pathway genes (EGFR, KRAS, HER2, and BRAF).
Using this assay, we confirmed that BRAF mutations can be identified in a minority of NSCLC tumors and that patients whose tumors harbor BRAF mutations have a distinct clinical profile compared with those whose tumors harbor kinase domain mutations in EGFR.
Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma.
The epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated with different frequencies in non-small cell lung cancer and mutations predict clinical response to EGFR inhibitors.