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 Thyroid Cancer
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
AKAP-BRAF Translocation in Thyroid Cancer
|Location of mutation
||Chromosomal rearrangements involving the BRAF gene
|Frequency of AKAP-BRAF translocation in papillary thyroid cancer
and Nikiforov 2005)
|Frequency of AKAP-BRAF translocation in thyroid cancer associated with radiation
||Up to 11% (Ciampi and Nikiforov 2005)
|Implications for Targeted Therapeutics
|Response to non-specific BRAF inhibitors
||Unknown at this time
|Response to mutant-specific BRAF inhibitors
||Unknown at this time
AKAP9-BRAF translocation fuses the first 8 exons of the A-kinase
anchor protein 9 (AKAP9) gene with the C-terminal region (exons 9–18)
of BRAF. The rearrangement, which leads to constitutive activation
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.
Fusco, Viglietto, and
tumors with AKAP9-BRAF fusions respond to BRAF inhibitors is
unknown at this time.
Suggested Citation: Espinosa, A., J. Gilbert. 2015. AKAP-BRAF Translocation in
Thyroid Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/thyroid-cancer/braf/125/
(Updated February 17).
Last Updated: February 17, 2015
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