Ryohei Katayama.

Total RNA was extracted from tumor tissue, and the sequencing of an RT-PCR product spanning the CD74ROS1 fusion junction revealed a c.Gly2032Arg , mutation that had not been detected in the pretreatment specimen . Following the patient died, an autopsy was performed. All of the sites of disease that were examined had the G2032R mutation , suggesting that its occurrence was an early on event in the clonal growth of crizotinib-resistant tumor cells. S2 in the Supplementary Appendix). S2 in the Supplementary Appendix). No mutations in EGFR or KRAS had been detected on exon sequencing.). To determine whether an arginine substitution as of this conserved residue conferred resistance to ROS1 inhibitors extremely, we transfected 293T cells with an expression plasmid encoding either G2032R or nonmutated CD74ROS1.Last data were used in the University of Leuven, Belgium, for independent statistical evaluation. The initial and last authors wrote the first draft of the manuscript, and the executive and steering committees participated on paper subsequent drafts. The last author vouches for the precision of the data and for the fidelity of the report to the analysis protocol. The decision to send the manuscript for publication was made by the executive committee and authorized by the sponsor. The study protocol was approved by national regulatory authorities along with the regional ethics committee at each study center.