187Alfred K. Lam (ed.), Esophageal Adenocarcinoma: Methods and Protocols, Methods in Molecular Biology, vol. 1756,
https://doi.org/10.1007/978-1-4939-7734-5_17, © Springer Science+Business Media, LLC 2018
Chapter 17
Liquid Biopsy for Investigation of Cancer DNA
in Esophageal Adenocarcinoma: Cell-Free Plasma
DNA and Exosome-Associated DNA
Robert A. Smith and Alfred K. Lam
Abstract
Liquid biopsy of cancers is an area of increasing interest in medical practice for the surveillance, manage-
ment, and potential detection of malignant cells, using minimally invasive collection of body fluids. A liq-
uid biopsy is particularly useful for metastatic cancers, which may be difficult to be sampled by core biopsy,
due to difficulty of access or an occult location. Access to DNA shed from esophageal adenocarcinoma can
enable the detection of mutations confirming the presence of malignant cells or the evolution of clonal
lines with altered treatment response profiles. In this chapter, we detail a method for the isolation of cell-
free DNA from blood plasma and DNA associated with exosomes in blood from patients with esophageal
adenocarcinoma.
Key words Liquid biopsy, Cell-free DNA, Exosome-associated DNA, Cancer surveillance, Cancer
detection, Cancer management, Mutations1 Introduction
Esophageal adenocarcinoma, like other cancers, arises due to the
development of genetic mutations in affected tissues, and there is
considerable interest in using the detection of these mutations as
diagnostic and prognostic markers for the disease [ 1 , 2 ].
Detection of cancer can be difficult, particularly in tissues
where a tumor may not be noticed until significant growth and
proliferation of mutant sub-lineages has occurred (such as in
esophageal adenocarcinoma). It is a major challenge to public
health and the management of individual patients. Similarly, iden-
tifying mutations that have arisen in cancer tissues that are difficult
to access for physical biopsy is a challenge and equally as useful for
the provision of targeted therapy and general patient management.
The solution to both of these challenges is to make use of a liquid
biopsy, sampling tumor DNA or RNA derived from circulating
tumor cells, apoptotic or necrotic cancer cells or cancer exosomes,