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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...
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Published in: | Genes chromosomes & cancer 2005-03, Vol.42 (3), p.269-279 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. © 2004 Wiley‐Liss, Inc. |
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ISSN: | 1045-2257 1098-2264 |
DOI: | 10.1002/gcc.20147 |