Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer

Barault, Ludovic;Amatu, Alessio;Siravegna, Giulia;Ponzetti, Agostino;Moran, Sebastian;Cassingena, Andrea;Mussolin, Benedetta;Falcomatà, Chiara;Binder, Alexandra M;Cristiano, Carmen;Oddo, Daniele;Guarrera, Simonetta;Cancelliere, Carlotta;Bustreo, Sara;Bencardino, Katia;Maden, Sean;Vanzati, Alice;Zavattari, Patrizia;Matullo, Giuseppe;Truini, Mauro;Grady, William M;Racca, Patrizia;Michels, Karin B;Siena, Salvatore;Esteller, Manel;Bardelli, Alberto;Sartore-Bianchi, Andrea;Di Nicolantonio, Federica

2018-01-01

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Abstract

Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC).