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Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.

Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells / Malara, N.; Coluccio, M. L.; Limongi, T.; Asande, M.; Trunzo, V.; Cojoc, G.; Raso, C.; Candeloro, P.; Perozziello, G.; Raimondo, R.; De Vitis, S.; Roveda, L.; Renne, M.; Prati, U.; Mollace, V.; Di Fabrizio, E.. - In: SMALL. - ISSN 1613-6810. - 10:21(2014), pp. 4324-4331. [10.1002/smll.201400498]

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