Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma

• Main Authors: Sascha Hoppe, Christoph Jonas, Marten Christian Wenzel, Oscar Velazquez Camacho, Christoph Arolt, Yue Zhao, Reinhard Büttner, Alexander Quaas, Patrick Sven Plum, Axel Maximilian Hillmer
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Cancers
• Subjects: esophageal adenocarcinoma; genomics; transcriptomics; mutation; tumor development; Barrett’s esophagus
• Online Access: https://www.mdpi.com/2072-6694/13/17/4300

Esophageal adenocarcinoma (EAC) is a deadly disease with limited options for targeted therapy. With the help of next-generation sequencing studies over the last decade, we gained an understanding of the genomic architecture of EAC. The tumor suppressor gene <i>TP53</i> is mutated in 70 to 80% of tumors followed by genomic alterations in <i>CDKN2A</i>, <i>KRAS</i>, <i>ERBB2</i>, <i>ARID1A</i>, <i>SMAD4</i> and a long tail of less frequently mutated genes. EAC is characterized by a high burden of point mutations and genomic rearrangements, resulting in amplifications and deletions of genomic regions. The genomic complexity is likely hampering the efficacy of targeted therapies. Barrett’s esophagus (BE), a metaplastic response of the esophagus to gastro-esophageal reflux disease, is the main risk factor for the development of EAC. Almost all EACs are derived from BE. The sequence from BE to EAC provides an opportunity to study the genomic evolution towards EAC. While the overlap of point mutations between BE and EAC within the same patient is, at times, surprisingly low, there is a correlation between the complexity of the genomic copy number profile and the development of EAC. Transcriptomic analyses separated EAC into a basal and a classical subtype, with the basal subtype showing a higher level of resistance to chemotherapy. In this review, we provide an overview of the current knowledge of the genomic and transcriptomic characteristics of EAC and their relevance for the development of the disease and patient care.