BRAF belongs to a family of serine-threonine protein
kinases that includes ARAF, BRAF, and CRAF
(RAF1). RAF kinases are central mediators in
the MAP kinase signaling cascade and exert
their effect predominantly through phosphorylation
and activation of MEK. This occurs following the dimerization
(hetero- or homo-) of the RAF molecules. As part of the MAP kinase pathway, RAF is involved in many cellular processes,
including cell proliferation, differentiation, and transcriptional regulation.
Mutant BRAF has been implicated in the pathogenesis of several cancers, including melanoma,
non-small cell lung cancer, colorectal cancer, papillary thyroid cancer, and ovarian cancer (Davies et al.
2002). Mutant BRAF has been observed in these cancers as well as glioma and
gastrointestinal stromal tumor (GIST).
Figure 1. Schematic of the MAPK and PI3K
pathways. Growth factor binding to receptor
tyrosine kinase results in activation of the
MAPK signaling pathway (RAS-RAF-MEK-ERK) and
the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.
Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. BRAF. My Cancer
(Updated December 7).
Last Updated: December 7, 2015
BRAF in Non-Small Cell Lung Cancer (NSCLC)
Somatic mutations in BRAF have
been found in 1–4% of all NSCLC (Brose et al. 2002; Cardarella et al. 2013;
Davies et al. 2002;
al. 2002; Paik et al. 2011; Pratilas et al. 2008),
most of which are adenocarcinomas. BRAF mutations are more likely to be found in
former/current smokers (Paik et al. 2011; Pratilas et al. 2008)
In contrast to melanoma where the majority of BRAF mutations occur at valine 600 (V600) within exon 15 of the
kinase domain, BRAF mutations in
lung cancer also occur at other positions within the kinase domain. In one study of 697
patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%).
Of these 18 patients, the BRAF mutations identified were V600E (50%), G469A (39%),
and D594G (11%; Paik
et al. 2011).
In the vast majority of cases, BRAF mutations
are non-overlapping with other oncogenic mutations
found in NSCLC (e.g., EGFR mutations, ALK rearrangements, etc.).
Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. BRAF in Non-Small Cell
Lung Cancer (NSCLC). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/braf/
(Updated June 18).
Last Updated: June 18, 2015
My Cancer Genome has released its new and improved cancer clinical trials search tool on our
beta website. Please visit beta.padiracinnovation.org
to check it out!