JAK Pseudokinase Domain Variants Highlight nRTK VUSs Identified with Next-Generation Sequencing in Solid Tumor Patients
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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 . Tumor profiling with NGS enables the entire coding sequence of numerous genes to be evaluated, thus facilitating the identification of novel nsSNPs in nRTKs.
We reviewed advanced breast, colon and lung cancer patients treated at West Cancer Center (Memphis, Tennessee) from 2013 to 2015 who received tumor profiling including NGS with a 592 cancer-related gene panel from Caris Life Sciences (Phoenix, Arizona). Caris NGS searched 14 nRTKs: ABL1, ABL2, AKT1, AKT2, AKT3, BTK, JAK1, JAK2, JAK3, SRC, CDK4, CDK6, CDK12, PIK3CA. All mutations...