Nilsson, R. Jonas A.Karachaliou, NikiBerenguer, JordiGimenez-Capitan, AnaSchellen, PepijnTeixido, CristinaTannous, JihaneKuiper, Justine L.Drees, EstherGrabowska, Magdavan Keulen, MarteHeideman, Danielle A.M.Thunnissen, ErikDingemans, Anne-Marie C.Viteri, SantiagoTannous, BakhosDrozdowskyj, AnaRosell, RafaelSmit, Egbert F.Wurdinger, Thomas2016-05-022016Nilsson, R. J. A., N. Karachaliou, J. Berenguer, A. Gimenez-Capitan, P. Schellen, C. Teixido, J. Tannous, et al. 2016. “Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer.” Oncotarget 7 (1): 1066-1075.1949-2553http://nrs.harvard.edu/urn-3:HUL.InstRepos:26859974Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.en-USdiagnosticsNSCLCliquid biopsiesplateletsEML4-ALKJournal Article2016-05-0210.18632/oncotarget.6279