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Article

Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients

1
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy
2
Oncological Surgery, Veneto Institute of Oncology IOV-IRCCS, via dei Carpani 16, 31033 Castelfranco Veneto, Italy
3
Endoscopy Unit, Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padova, Italy
4
Department of Medicine (DIMED), Surgical Pathology and Cytopathology, University of Padova, via Giustiniani 2, 35128 Padova, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1547; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041547
Received: 18 December 2019 / Revised: 13 February 2020 / Accepted: 21 February 2020 / Published: 24 February 2020
(This article belongs to the Special Issue Pathophysiology of Esophageal Adenocarcinoma)
DNA methylation plays an important role in cancer development. Cancer cells exhibit two types of DNA methylation alteration: site-specific hypermethylation at promoter of oncosuppressor genes and global DNA hypomethylation. This study evaluated the methylation patterns of long interspersed nuclear element (LINE-1) sequences which, due to their relative abundance in the genome, are considered a good surrogate indicator of global DNA methylation. LINE-1 methylation status was investigated in the cell-free DNA (cfDNA) of 21 patients, 19 with esophageal adenocarcinoma (EADC) and 2 with Barrett’s esophagus (BE). The two BE patients and one EADC patient were also analyzed longitudinally. Methylation status was analyzed using restriction enzymes and DNA amplification. This methodology was chosen to avoid bisulfite conversion, which we considered inadequate for cfDNA analysis. Indeed, cfDNA is characterized by poor quality and low concentration, and bisulfite conversion might worsen these conditions. Results showed that hypomethylated LINE-1 sequences are present in EADC cfDNA. Furthermore, longitudinal studies in BE suggested a correlation between methylation status of LINE-1 sequences in cfDNA and progression to EADC. In conclusion, our study indicated the feasibility of our methodological approach to detect hypomethylation events in cfDNA from EADC patients, and suggests LINE-1 methylation analysis as a new possible molecular assay to integrate into patient monitoring. View Full-Text
Keywords: LINE-1 hypomethylation; Barrett’s esophagus (BE); Esophageal adenocarcinoma (EADC); cfDNA; liquid biopsy LINE-1 hypomethylation; Barrett’s esophagus (BE); Esophageal adenocarcinoma (EADC); cfDNA; liquid biopsy
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MDPI and ACS Style

Boldrin, E.; Curtarello, M.; Dallan, M.; Alfieri, R.; Realdon, S.; Fassan, M.; Saggioro, D. Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients. Int. J. Mol. Sci. 2020, 21, 1547. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041547

AMA Style

Boldrin E, Curtarello M, Dallan M, Alfieri R, Realdon S, Fassan M, Saggioro D. Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients. International Journal of Molecular Sciences. 2020; 21(4):1547. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041547

Chicago/Turabian Style

Boldrin, Elisa, Matteo Curtarello, Marco Dallan, Rita Alfieri, Stefano Realdon, Matteo Fassan, and Daniela Saggioro. 2020. "Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients" International Journal of Molecular Sciences 21, no. 4: 1547. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041547

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