Mondelo-Macia, PatriciaRodriguez-Lopez, CarmelaValina, LauraAguin, SantiagoLeon-Mateos, LuisGarcia-Gonzalez, JorgeAbalo, AliciaRapado-Gonzalez, OscarSuarez-Cunqueiro, MercedesDiaz-Lagares, AngelCuriel, TeresaCalabuig-Farinas, SilviaAzkárate, AitorObrador-Hevia, AntoniaAbdulkader, IhabMuinelo-Romay, LauraDiaz-Pena, RobertoLopez-Lopez, Rafael2024-09-132024-09-132020-02Mondelo-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.http://hdl.handle.net/20.500.13003/11887https://hdl.handle.net/20.500.12105/22940MET 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.enghttp://creativecommons.org/licenses/by/4.0/MET protein expressionMET amplificationCirculating free DNA (cfDNA)Circulating tumor cells (CTCs)Targeted therapyMET copy numberCase-Control StudiesHumansErbB ReceptorsAntineoplastic AgentsLiquid BiopsyProtein Kinase InhibitorsNeoplasmsMaleProspective StudiesGene DosageProto-Oncogene Proteins c-metBiomarkers, TumorFemaleNeoplastic Cells, CirculatingDrug Resistance, NeoplasmCell-Free Nucleic AcidsRetrospective Studiesresearch articleAttribution 4.0 International321024869252210.3390/cells90205222073-4409Cellsopen accessResistencia a AntineoplásicosBiopsia LíquidaCélulas Neoplásicas CirculantesProteínas Proto-Oncogénicas c-metInhibidores de Proteínas QuinasasÁcidos Nucleicos Libres de CélulasFemeninoDosificación de GenBiomarcadores de TumorReceptores ErbBMasculinoAntineoplásicosHumanosNeoplasiasEstudios ProspectivosEstudios RetrospectivosEstudios de Casos y Controles2-s2.0-85090997076521944900263L2003836435