Abstract
Tyrosine kinases, which are important regulators of intracellular signal-transduction pathways, have mutated forms that are often associated with oncogenesis and are attractive targets for therapeutic intervention. Recently, systematic mutational analyses of tyrosine kinases revealed that a minimum of 30% of colorectal cancer contain at least one mutation in the tyrosine kinases. To further explore these mutations, we examined all reported mutations of NTRK3, FES, KDR, EPHA3, NTRK2, JAK1, PDGFRA, EPHA7, EPHA8, ERBB4, FGFR1, MLK4 and GUCY2F genes in the 24 colorectal cancer cell lines. Unexpectedly, among 24 colorectal cancer cell lines, only two cell lines (LoVo and CaR1) harbored mutation C1408T (R470C) in MLK4 gene. The mutation rate was extremely low compared to that previously reported. Therefore, we analyzed mutations in 46 colorectal cancer samples resected from the same number of Japanese patients. Surprisingly, none of the 46 samples contained any of the mutations reported. Based on our study, we advise that a more comprehensive tyrosine kinase gene mutation assay is necessary in the future.
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Acknowledgements
We thank Mitsuko Tsubouchi for technical assistance, and we are also grateful to many colleagues for the helpful discussions during the course of this work. This work was supported in part by the Grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Shao, RX., Kato, N., Lin, LJ. et al. Absence of tyrosine kinase mutations in Japanese colorectal cancer patients. Oncogene 26, 2133–2135 (2007). https://doi.org/10.1038/sj.onc.1210007
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DOI: https://doi.org/10.1038/sj.onc.1210007
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