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Front. Genet. | doi: 10.3389/fgene.2018.00006

Development of a method to implement Whole-Genome Bisulfite Sequencing of cfDNA from Cancer Patients and a Mouse Tumor Model

Elaine C. Maggi1, Silvia Gravina2, Haiying Cheng3, Bilal Piperdi3, Ziqiang Yuan4, Xiao Dong1, Steven K. Libutti4, Jan Vijg5 and  Cristina Montagna6*
  • 1Department of Genetics, Albert Einstein College of Medicine, United States
  • 2Illumina (United States), United States
  • 3Department of Medicine, Albert Einstein College of Medicine, United States
  • 4Rutgers Cancer Institute of New Jersey, United States
  • 5Department of Genetics, Ophthalmology and Visual Science, and Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine, United States
  • 6Department of Genetics and Pathology, Albert Einstein College of Medicine, United States

The goal of this study was to develop a method for whole genome cell-free DNA (cfDNA) methylation analysis in humans and mice with the ultimate goal to facilitate the identification of tumor derived DNA methylation changes in the blood. Plasma or serum from patients with pancreatic neuroendocrine tumors or lung cancer, and plasma from a murine model of pancreatic adenocarcinoma was used to develop a protocol for cfDNA isolation, library preparation and whole genome bisulfite sequencing (WGBS) of ultra low quantities of cfDNA, including tumor-specific DNA. The protocol developed produced high quality libraries consistently generating a conversion rate >98% that will be applicable for the analysis of human and mouse plasma or serum to detect tumor-derived changes in DNA methylation.

Keywords: cell-free DNA, cfDNA, DNA Methylation, biomarker, Pancreatic Cancer, Circulating DNA, non-invasive blood based screening, mouse cfDNA

Received: 03 Aug 2017; Accepted: 05 Jan 2018.

Edited by:

Ingrid A. Hedenfalk, Lund University, Sweden

Reviewed by:

Mariana Brait, Johns Hopkins University, United States
Shicheng Guo, University of California, San Diego, United States  

Copyright: © 2018 Maggi, Gravina, Cheng, Piperdi, Yuan, Dong, Libutti, Vijg and Montagna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Cristina Montagna, Albert Einstein College of Medicine, Department of Genetics and Pathology, 1300 Morris Park Ave, New York City, 10461, New York, United States, cristina.montagna@einstein.yu.edu