Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma
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 t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4300 |
| _version_ | 1797521625512411136 |
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| author | Sascha Hoppe Christoph Jonas Marten Christian Wenzel Oscar Velazquez Camacho Christoph Arolt Yue Zhao Reinhard Büttner Alexander Quaas Patrick Sven Plum Axel Maximilian Hillmer |
| author_facet | Sascha Hoppe Christoph Jonas Marten Christian Wenzel Oscar Velazquez Camacho Christoph Arolt Yue Zhao Reinhard Büttner Alexander Quaas Patrick Sven Plum Axel Maximilian Hillmer |
| author_sort | Sascha Hoppe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:15:11Z |
| format | Article |
| id | doaj.art-f1e1bb2d7d344674a9782e124d0afc21 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:15:11Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f1e1bb2d7d344674a9782e124d0afc212023-11-22T10:25:13ZengMDPI AGCancers2072-66942021-08-011317430010.3390/cancers13174300Genomic and Transcriptomic Characteristics of Esophageal AdenocarcinomaSascha Hoppe0Christoph Jonas1Marten Christian Wenzel2Oscar Velazquez Camacho3Christoph Arolt4Yue Zhao5Reinhard Büttner6Alexander Quaas7Patrick Sven Plum8Axel Maximilian Hillmer9Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyDepartment of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyInstitute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyEsophageal 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.https://www.mdpi.com/2072-6694/13/17/4300esophageal adenocarcinomagenomicstranscriptomicsmutationtumor developmentBarrett’s esophagus |
| spellingShingle | Sascha Hoppe Christoph Jonas Marten Christian Wenzel Oscar Velazquez Camacho Christoph Arolt Yue Zhao Reinhard Büttner Alexander Quaas Patrick Sven Plum Axel Maximilian Hillmer Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma Cancers esophageal adenocarcinoma genomics transcriptomics mutation tumor development Barrett’s esophagus |
| title | Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma |
| title_full | Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma |
| title_fullStr | Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma |
| title_full_unstemmed | Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma |
| title_short | Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma |
| title_sort | genomic and transcriptomic characteristics of esophageal adenocarcinoma |
| topic | esophageal adenocarcinoma genomics transcriptomics mutation tumor development Barrett’s esophagus |
| url | https://www.mdpi.com/2072-6694/13/17/4300 |
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