Signaling by BRAF and RAF1 fusions

Stable Identifier
Homo sapiens
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In addition to the more prevalent point mutations, BRAF and RAF1 are also subject to activation as a result of translocation events that yield truncated or fusion products (Jones et al, 2008; Cin et al, 2011; Palanisamy et al, 2010; Ciampi et al, 2005; Stransky et al, 2014; Hutchinson et al, 2013; Zhang et al, 2013; Lee et al, 2012; Ricarte-Filho et al, 2013; reviewed in Lavoie and Therrien et al, 2015). In general these events put the C-terminal kinase domain of BRAF or RAF1 downstream of an N-terminal sequence provided by a partner protein. This removes the N-terminal region of the RAF protein, relieving the autoinhibition imposed by this region of the protein. In addition, some but not all of the fusion partner proteins have been shown to contain coiled-coil or other dimerization domains. Taken together, the fusion proteins are thought to dimerize constitutively and activate downstream signaling (Jones et al, 2008; Lee et al, 2012; Hutchinson et al, 2013; Ciampi et al, 2005; Cin et al, 2011; Stransky et al, 2014).

Literature References
PubMed ID Title Journal Year
24345920 BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition

Hutchinson, KE, Lyle, PL, Puzanov, I, Sosman, JA, Pietenpol, JA, Lehmann, BD, Ross, JS, Lipson, D, Vnencak-Jones, CL, Stephens, PJ, Miller, VA, Otto, G, Pao, W

Clin. Cancer Res. 2013
15630448 Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer

Kerler, R, Fagin, JA, Rabes, HM, Nikiforov, YE, Knauf, JA, Gandhi, M, Ciampi, R, Zhu, Z, Nikiforova, MN

J. Clin. Invest. 2005
25907612 Regulation of RAF protein kinases in ERK signalling

Lavoie, H, Therrien, M

Nat. Rev. Mol. Cell Biol. 2015
21424530 Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma

Herr, R, Scheurlen, W, Jabado, N, Jacob, K, Gnekow, A, Collins, VP, Lichter, P, Pekrun, A, Falkenstein, F, Meyer, C, Remke, M, von Deimling, A, Witt, H, Korshunov, A, Pfister, SM, Marschalek, R, Cin, H, Bender, S, Benner, A, Omran, H, Olbrich, H, Van Anh, TN, Kulozik, AE, Witt, O, Lambert, S, Janzarik, WG, Brummer, T, Jones, DT

Acta Neuropathol. 2011
20526349 Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma

Shankar, S, Siddiqui, J, Kuefer, R, Chen, YB, Greenson, JK, Lafargue, CJ, Ramnarayanan, K, Han, B, Palanisamy, N, Demichelis, F, Esgueva, R, Dhanasekaran, SM, Giordano, TJ, Fullen, DR, Pflueger, D, Moeller, P, Rubin, MA, Maher, CA, Cao, Q, Cao, X, Ateeq, B, Banerjee, S, Bismar, TA, Tomlins, SA, Varambally, S, Kumar-Sinha, C, Chinnaiyan, AM, Johnson, TM, Suleman, K, Tan, P, Kalyana-Sundaram, S

Nat. Med. 2010
18974108 Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas

Collins, VP, Liu, L, Kocialkowski, S, Ichimura, K, Pearson, DM, B├Ącklund, LM, Jones, DT

Cancer Res. 2008
24135138 Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers

Fagin, JA, Thomas, GA, Viale, A, Ricarte-Filho, JC, Voza, F, Bogdanova, T, Knauf, JA, Montero-Conde, C, Li, S, Garcia-Rendueles, ME, Heguy, A, Mason, CE

J. Clin. Invest. 2013
25204415 The landscape of kinase fusions in cancer

Kim, JL, Schalm, S, Stransky, N, Lengauer, C, Cerami, E

Nat Commun 2014
22745804 A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation

Buckman, D, Pavlicek, A, Aparicio, S, Rejto, PA, Srinivasa, SP, Lee, NV, Ye, J, Ching, KA, Zhao, Y, Christensen, JG, Bagrodia, S, Lira, ME

PLoS ONE 2012
23583981 Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas

Lu, C, Dooling, DJ, Qaddoumi, I, Parker, M, Ellison, DW, Rusch, M, Easton, J, Miller, CP, Hedlund, E, Vadodaria, B, Downing, JR, Orisme, W, Tatevossian, RG, Wilson, RK, Wang, J, Zhao, D, Sheer, D, Kriwacki, R, Lee, R, Huether, R, Becksfort, J, Shurtleff, S, Wu, G, Boop, FA, Kandoth, C, Chen, X, Ma, J, Boggs, K, Baker, SJ, Gajjar, A, Fulton, RS, Mardis, ER, Fulton, LL, Gilbertson, RJ, Cheng, J, Wei, L, Tang, B, Punchihewa, C, Dalton, JD, Song, G, Mulder, HL, Ochoa, K, Ding, L, Tang, C, Nagahawatte, P, Mullighan, CG, Zhang, J, Li, Y

Nat. Genet. 2013
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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