Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hosoya, N. et al.

Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation.

The SRC family of kinases is rarely mutated in primary human tumors. We report the identification of a SRC-like tyrosine kinase gene, FRK ( Fyn-related kinase), fused with ETV6 in a patient with acute myelogenous leukemia carrying t(6;12)(q21;p13). Both reciprocal fusion transcripts, ETV6/ FRK and FRK/ETV6, were expressed. In ETV6/ FRK, exon 4 of ETV6 was fused in-frame to exon 3 of FRK, producing a chimeric protein consisting of the entire oligomerization domain of ETV6 and the kinase domain of FRK. The ETV6/ FRK protein was shown to be constitutively autophosphorylated on its tyrosine residues. ETV6/ FRK phosphorylated histones H2B and H4 in vitro to a greater extent than did FRK, suggesting it had elevated kinase activity. ETV6/ FRK could transform both Ba/F3 cells and NIH3T3 cells, which depended on its kinase activity. Moreover, ETV6/ FRK inhibited ETV6-mediated transcriptional repression in a dominant-negative manner. This report provides the first evidence that a SRC-like kinase gene, FRK fused with ETV6, could directly contribute to leukemogenesis by producing an oncoprotein, ETV6/ FRK, with dual functions: constitutive activation of the ETV6/ FRK tyrosine kinase and dominant-negative modulation of ETV6-mediated transcriptional repression.[1]

References

Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation. Hosoya, N., Qiao, Y., Hangaishi, A., Wang, L., Nannya, Y., Sanada, M., Kurokawa, M., Chiba, S., Hirai, H., Ogawa, S. Genes Chromosomes Cancer (2005) [Pubmed]

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