No incidence of BRAF mutations in salivary gland carcinomasImplications for anti-EGFR Therapies

Abstract

BRAF is the main effector of KRAS in the RAS-RAF-MAPK axis, a signaling pathway downstream of EGFR. The activation of this cascade is an important pathway in cancer development and is considered a key pathway for therapeutic molecules. Recent studies in metastatic colorectal cancer found that an oncogenic activation of BRAF by a point mutation in exon 15 (V600E) could bypass the EGFR-initiated signaling cascade with the effect that patients bearing the mutant BRAF allele are not likely to benefit from EGFR-targeted therapies. We designed an allele-specific PCR and screened 65 salivary gland carcinoma (SGC) of the main histopathological types for the BRAF V600E mutation. All 65 SGC in this cohort (100) presented the BRAF wildtype. In a previous study, we found a KRAS wildtype in 98.5 of SGC. These findings imply that SGC rarely acquires mutations that result in a constitutive activation of the signaling cascade downstream of EGFR and this pleads in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies. Copyright © 2009 Regine Dahse et al.