A new mechanism of BRAF activation in human thyroid papillary carcinomas.
In this issue of the JCI, Ciampi et al. report the identification of a novel oncogene in patients affected by radiation-associated thyroid papillary carcinomas. This oncogene derives from a paracentric inversion of the long arm of chromosome 7, which results in an in-frame fusion of the N-terminus of the A-kinase anchor protein 9 (AKAP9) gene with the C-terminal catalytic domain (exons 9-18) of the serine-threonine kinase BRAF. The resulting AKAP9-BRAF fusion protein shows constitutive kinase activity, and it is able to transmit mitogenic signals to the MAPK pathways and to promote malignant transformation of NIH3T3 cells.
Fusco
Alfredo
A
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II, Naples, Italy. afusco@napoli.com
Viglietto
Giuseppe
G
Santoro
Massimo
M
D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D047852:Chernobyl Nuclear Accident; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D009857:Oncogenes / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D011993:Recombinant Fusion Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf