BRAF kinase activation via chromosomal rearrangement in radiation-induced and sporadic thyroid cancer.

摘要: Activating point mutations of the BRAF gene have been recently described in a variety human tumors. In study published Journal Clinical Investigation, we reported novel mechanism activation this via paracentric inversion chromosome 7q. The fusion protein, AKAP9-BRAF, contains intact kinase domain and lacks autoinhibitory N-terminal portion BRAF. It exhibited constitutive was transforming for NIH3T3 cells. This finding represents first demonstration RAF by chromosomal rearrangement AKAP9-BRAF more common radiation-induced thyroid tumors, whereas predominated sporadic tumors same type, demonstrating association between environmental factors specific mechanisms activation.