Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma
Up to 40% of esophageal carcinomas have a biallelic intact TP53 gene. It is largely unclear how these carcinoma cells prevent apoptosis, what is the kind of pathway alterations, or whether therapeutically relevant alterations exist in this subgroup. We evaluated The Cancer Genome Atlas (TCGA) data t...
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doaj-fd71081f44904888a396b25fabbceff42020-11-25T00:35:49ZengElsevierTranslational Oncology1936-52332019-01-01121154161Genomic Characterization of TP53–Wild-Type Esophageal CarcinomaAlexander Quaas0Carina Heydt1Florian Gebauer2Hakan Alakus3Heike Loeser4Reinhard Buettner5Axel Hillmer6Christiane Bruns7Sabine Merkelbach-Bruse8Thomas Zander9Peter Frommolt10Institute of Pathology, University of Cologne, Germany; Address all correspondence to: Alexander Quaas, Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.Institute of Pathology, University of Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, GermanyInstitute of Pathology, University of Cologne, GermanyInstitute of Pathology, University of Cologne, GermanyInstitute of Pathology, University of Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, GermanyInstitute of Pathology, University of Cologne, GermanyDepartment I of Internal Medicine, Center for Integrated Oncology (CIO), University of Cologne, GermanyIndivumed Group, Hamburg, GermanyUp to 40% of esophageal carcinomas have a biallelic intact TP53 gene. It is largely unclear how these carcinoma cells prevent apoptosis, what is the kind of pathway alterations, or whether therapeutically relevant alterations exist in this subgroup. We evaluated The Cancer Genome Atlas (TCGA) data to compare TP53-mutated with TP53–wild-type tumors regarding copy number variations, gene mutations, and expression patterns of protein-coding genes and miRNAs. Additionally, we analyzed up to 428 esophageal adenocarcinomas (EACs) in total using an ultra-deep parallel sequencing panel, immunohistochemistry, as well as fluorescence in situ hybridization. In the TCGA cohort, 17.3% has a biallelic intact TP53 gene. This group has a smaller average total size of somatic copy number variations. Some protein coding genes and miRNAs were differentially expressed between the TP53-wild-type and TP53-mutated group to emphasize mdm2, CCND2, TP73, or miRNA 150, 488, or 4662a. In addition, 50% of the TP53–wild-type tumors carry somatic mutations in at least one of the genes involved in the TP53 pathway. Our patient cohort revealed 41.3% TP53–wild-type tumors; 5.6% were MDM2 amplified. In accordance with the TCGA data, we did not find a prognostic relevance of TP53 in our tumor cohort as well. The mutation status of TP53 defines an important subtype in esophageal carcinoma. Our comprehensive molecular analysis revealed important and potentially therapeutically relevant genomic alterations in this subgroup.http://www.sciencedirect.com/science/article/pii/S1936523318303899 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexander Quaas Carina Heydt Florian Gebauer Hakan Alakus Heike Loeser Reinhard Buettner Axel Hillmer Christiane Bruns Sabine Merkelbach-Bruse Thomas Zander Peter Frommolt |
spellingShingle |
Alexander Quaas Carina Heydt Florian Gebauer Hakan Alakus Heike Loeser Reinhard Buettner Axel Hillmer Christiane Bruns Sabine Merkelbach-Bruse Thomas Zander Peter Frommolt Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma Translational Oncology |
author_facet |
Alexander Quaas Carina Heydt Florian Gebauer Hakan Alakus Heike Loeser Reinhard Buettner Axel Hillmer Christiane Bruns Sabine Merkelbach-Bruse Thomas Zander Peter Frommolt |
author_sort |
Alexander Quaas |
title |
Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma |
title_short |
Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma |
title_full |
Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma |
title_fullStr |
Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma |
title_full_unstemmed |
Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma |
title_sort |
genomic characterization of tp53–wild-type esophageal carcinoma |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2019-01-01 |
description |
Up to 40% of esophageal carcinomas have a biallelic intact TP53 gene. It is largely unclear how these carcinoma cells prevent apoptosis, what is the kind of pathway alterations, or whether therapeutically relevant alterations exist in this subgroup. We evaluated The Cancer Genome Atlas (TCGA) data to compare TP53-mutated with TP53–wild-type tumors regarding copy number variations, gene mutations, and expression patterns of protein-coding genes and miRNAs. Additionally, we analyzed up to 428 esophageal adenocarcinomas (EACs) in total using an ultra-deep parallel sequencing panel, immunohistochemistry, as well as fluorescence in situ hybridization. In the TCGA cohort, 17.3% has a biallelic intact TP53 gene. This group has a smaller average total size of somatic copy number variations. Some protein coding genes and miRNAs were differentially expressed between the TP53-wild-type and TP53-mutated group to emphasize mdm2, CCND2, TP73, or miRNA 150, 488, or 4662a. In addition, 50% of the TP53–wild-type tumors carry somatic mutations in at least one of the genes involved in the TP53 pathway. Our patient cohort revealed 41.3% TP53–wild-type tumors; 5.6% were MDM2 amplified. In accordance with the TCGA data, we did not find a prognostic relevance of TP53 in our tumor cohort as well. The mutation status of TP53 defines an important subtype in esophageal carcinoma. Our comprehensive molecular analysis revealed important and potentially therapeutically relevant genomic alterations in this subgroup. |
url |
http://www.sciencedirect.com/science/article/pii/S1936523318303899 |
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