JAK Pseudokinase Domain Variants Highlight nRTK VUSs Identified with Next-Generation Sequencing in Solid Tumor Patients

[摘要] Non-receptor tyrosine kinase (nRTK) pathways are aberrantly activated in cancer, and mutations in nRTKs have potential therapeutic and prognostic importance. Consisting of 10 families, the 32 known human nRTKs each include a TKD made of N and C-terminal lobes necessary for catalytic activity, as well as varying regulatory regions including Src homology 2 (SH2) and 3 (SH3), and in the case of the Janus kinases a PSKD which is also bi-lobed [1]. Tumor profiling with NGS enables the entire coding sequence of numerous genes to be evaluated, thus facilitating the identification of novel nsSNPs in nRTKs.