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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2016; 22(7): 2284-2293
Published online Feb 21, 2016. doi: 10.3748/wjg.v22.i7.2284
Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing
Yasushi Sasaki, Miyuki Tamura, Ryota Koyama, Takafumi Nakagaki, Yasushi Adachi, Takashi Tokino
Yasushi Sasaki, Miyuki Tamura, Ryota Koyama, Takafumi Nakagaki, Takashi Tokino, Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo 060-8556, Japan
Yasushi Adachi, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
Author contributions: Sasaki Y designed the report, analyzed the data and wrote the manuscript; Tamura M, Koyama R and Nakagaki T analyzed the data; Adachi Y and Tokino T edited the manuscript.
Supported by MEXT KAKENHI, Grant No. 221S0001.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yasushi Sasaki, MD, PhD, Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, S-1, W-17, Chuo-ku, Sapporo 060-8556, Japan. yasushi@sapmed.ac.jp
Telephone: +81-11-6112111-2410 Fax: +81-11-6183313
Received: July 28, 2015
Peer-review started: July 30, 2015
First decision: September 9, 2015
Revised: September 29, 2015
Accepted: December 19, 2015
Article in press: December 19, 2015
Published online: February 21, 2016
Abstract

Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett’s esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC.

Keywords: Esophageal squamous cell carcinoma, Next-generation sequencing, Somatic mutation, Driver mutation, Copy number variant

Core tip: Because targeted therapies have not been implemented in the treatment of esophageal squamous cell carcinoma (ESCC) to date, defining the genetic landscape of ESCC would facilitate the use of targeted therapies. Improvements in molecular profiling technologies have provided new insight into the basic molecular events during carcinogenesis as well as the mechanisms of anti-cancer drug resistance. Our invited review offers a current overview of the somatic genetic alterations in ESCC, emphasizing the recent results of large-scale sequencing efforts using next-generation sequencing technology.