CRAF mutations in lung cancer can be oncogenic and predict sensitivity to combined type II RAF and MEK inhibition.

ABSTRACT: Two out of 41 non-small cell lung cancer patients enrolled in a clinical study were found with a somatic CRAF mutation in their tumor, namely CRAF^P261A and CRAF^P207S. To our knowledge, both mutations are novel in lung cancer and CRAF^P261A has not been previously reported in cancer. Expression of CRAF^P261A in HEK293T cells and BEAS-2B lung epithelial cells led to increased ERK pathway activation in a dimer-dependent manner, accompanied with loss of CRAF phosphorylation at the negative regulatory S259 residue. Moreover, stable expression of CRAF^P261A in mouse embryonic fibroblasts and BEAS-2B cells led to anchorage-independent growth. Consistent with a previous report, we could not observe a gain-of-function with CRAF^P207S. Ty

SUBMITTER: Noeparast A 

PROVIDER: S-EPMC6756226 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature