Esophageal Adenocarcinoma Methods and Protocols

213

Alfred K. Lam (ed.), Esophageal Adenocarcinoma: Methods and Protocols, Methods in Molecular Biology, vol. 1756,
https://doi.org/10.1007/978-1-4939-7734-5_19, © Springer Science+Business Media, LLC 2018

Chapter 19

Targeted Single Gene Mutation in Esophageal

Adenocarcinoma

Katherine T. W. Lee, Robert A. Smith, Vinod Gopalan, and Alfred K. Lam

Abstract

Esophageal adenocarcinoma is heterogeneous and studies have reviewed many important mutations that
contribute to the pathogenesis of the cancer. These discoveries have helped paved the way into identifying
new gene markers or gene targets to develop novel molecular directed therapy for better patient outcomes
in esophageal adenocarcinoma. Despite the recent bloom in next-generation sequencing, Sanger sequenc-
ing still represents the gold standard method for the study of the driver genes in esophageal adenocarci-
noma. This chapter focuses on the sequencing techniques in identification of single gene mutations.

Key words Esophageal adenocarcinoma, Sanger sequencing, Targeted, Gene, Mutation

1 Introduction

Throughout the last decade or so, a major effort has been placed

into identifying novel mutations in esophageal adenocarcinoma

(EAC) in hopes of improving patient outcome. Many research

found that esophageal adenocarcinoma is highly mutated and

highly heterogeneous [ 1 – 3 ] with a huge amount of new tumor

suppressor genes [ 2 , 3 ], oncogenes [ 1 ], single nucleotide poly-

morphisms and copy number alterations [ 1 , 4 , 5 ]. These discover-

ies have helped in understanding the pathogenesis of esophageal

adenocarcinoma and identifying clinically relevant genomic altera-

tions. As a result, a new avenue for molecular directed therapy is

now within reach [ 5 ].

Genomic alteration could potentially be involved in the patho-

genesis of esophageal adenocarcinoma (Table 1 ). Patients with

V-Set and Immunoglobulin Domain Containing 10 Like

(VSIG10L) mutations (Table 1 ) showed increased susceptibility to

familial Barrett esophagus or esophageal adenocarcinoma [ 6 ].

Methylation of the gene Eye absent 4 (EYA4) was more frequently

observed in patients with esophageal adenocarcinoma, followed by

Barrett esophagus and subsequently, than in normal esophageal