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oai:repisalud.isciii.es:20.500.12105/229402024-11-28T19:28:08Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16966col_20.500.12105_16967

00925njm 22002777a 4500 dc Mondelo-Macia, Patricia author Rodriguez-Lopez, Carmela author Valina, Laura author Aguin, Santiago author Leon-Mateos, Luis author Garcia-Gonzalez, Jorge author Abalo, Alicia author Rapado-Gonzalez, Oscar author Suarez-Cunqueiro, Mercedes author Diaz-Lagares, Angel author Curiel, Teresa author Calabuig-Farinas, Silvia author Azkárate, Aitor author Obrador-Hevia, Antonia author Abdulkader, Ihab author Muinelo-Romay, Laura author Diaz-Pena, Roberto author Lopez-Lopez, Rafael author 2020-02 MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p <10(-10)) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch((R)) and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET+ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy. Mondelo-Macia P, Rodriguez-Lopez C, Valina L, Aguin S, Leon-Mateos L, Garcia-Gonzalez J, et al. Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients. Cells. 2020 Feb;9(2):522. 10.3390/cells9020522 2073-4409 Cells http://hdl.handle.net/20.500.13003/11887 32102486 L2003836435 2-s2.0-85090997076 https://hdl.handle.net/20.500.12105/22940 521944900263 MET protein expression MET amplification Circulating free DNA (cfDNA) Circulating tumor cells (CTCs) Targeted therapy MET copy number Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients