• What is BRAF?
  • BRAF in Thyroid Cancer
  • Clinical Trials


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.

Related Pathways

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. BRAF. My Cancer Genome https://www.padiracinnovation.org/content/disease/thyroid-cancer/braf/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

BRAF in Thyroid Cancer

Somatic mutations in BRAF have been found in 40–45% of papillary thyroid cancer (Kimura et al. 2003; Cohen et al. 2003; Ciampi et al. 2005). BRAF mutations are also found in anaplastic thyroid cancer (30–40%) and poorly differentiated tumors (20–40%; Namba et al. 2003; Nikiforova et al. 2003; Begum et al. 2004; Xing 2005; Ricarte-Filho et al. 2009).

The most prevalent BRAF mutations detected in thyroid cancers are missense mutations which introduce an amino acid substitution at valine 600. The vast majority (98%) of BRAF mutations are V600E (valine to glutamic acid). The result of these mutations is enhanced BRAF kinase activity and increased phosphorylation of downstream targets, particularly MEK (Wan et al. 2004).

The AKAP9-BRAF rearrangement is another mechanism of BRAF activation in thyroid cancers. This translocation, which fuses the first 8 exons of the A-kinase anchor protein 9 (AKAP9) gene with the C-terminal region (exons 9–18) of BRAF, is found in up to 11% of tumors associated with radiation exposure but in less than 1% of sporadic tumors (Ciampi et al. 2005; Fusco, Viglietto, and Santoro 2005).

Contributors: Allan V. Espinosa, M.D., Jill Gilbert, M.D.

Suggested Citation: Espinosa, A., J. Gilbert. 2015. BRAF in Thyroid Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/thyroid-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!

Disclaimer: The information presented at padiracinnovation.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.