{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:00:54Z","timestamp":1792555254372,"version":"4.5.0"},"reference-count":86,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["418074181"],"award-info":[{"award-number":["418074181"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1310, SP8"],"award-info":[{"award-number":["CRC 1310, SP8"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2020.119.1"],"award-info":[{"award-number":["2020.119.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70114428"],"award-info":[{"award-number":["70114428"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/cancers13174300","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:27:57Z","timestamp":1629970077000},"page":"4300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Sascha","family":"Hoppe","sequence":"first","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Jonas","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marten Christian","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Velazquez Camacho","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Arolt","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-3402","authenticated-orcid":false,"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"B\u00fcttner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Quaas","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8165-4553","authenticated-orcid":false,"given":"Patrick Sven","family":"Plum","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3381-7266","authenticated-orcid":false,"given":"Axel Maximilian","family":"Hillmer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1053\/j.gastro.2017.07.046","article-title":"The Epidemiology of Esophageal Adenocarcinoma","volume":"154","author":"Coleman","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrc2773","article-title":"Barrett\u2019s Oesophagus and Oesophageal Adenocarcinoma: Time for a new synthesis","volume":"10","author":"Reid","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11111","DOI":"10.1038\/ncomms11111","article-title":"Differential Clonal Evolution in Oesophageal Cancers in Response to Neo-adjuvant Chemotherapy","volume":"7","author":"Findlay","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1158\/2159-8290.CD-15-0412","article-title":"Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy","volume":"5","author":"Murugaesu","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1101\/gr.214296.116","article-title":"A Comparative Analysis of Whole Genome Sequencing of Esophageal Adenocarcinoma Pre- and Post-chemotherapy","volume":"27","author":"Noorani","year":"2017","journal-title":"Genome Res"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2017). Integrated Genomic Characterization of Oesophageal Carcinoma. Nature, 541, 169\u2013175.","DOI":"10.1038\/nature20805"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/ng.3659","article-title":"Mutational Signatures in Esophageal Adenocarcinoma Define Etiologically Distinct Subgroups with Therapeutic Relevance","volume":"48","author":"Secrier","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S1470-2045(17)30566-1","article-title":"Rilotumumab Plus Epirubicin, Cisplatin, and Capecitabine as First-line Therapy in Advanced MET-positive Gastric or Gastro-oesophageal junction cancer (RILOMET-1): A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial","volume":"18","author":"Catenacci","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huang, Z.H., Ma, X.W., Zhang, J., Li, X., Lai, N.L., and Zhang, S.X. (2018). Cetuximab for Esophageal Cancer: An Updated Meta-analysis of Randomized Controlled Trials. BMC. Cancer, 18.","DOI":"10.1186\/s12885-018-5040-z"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1200\/JCO.2011.36.2236","article-title":"Bevacizumab in Combination with Chemotherapy as First-line Therapy in Advanced Gastric Cancer: A randomized, double-blind, Placebo-controlled Phase III Study","volume":"29","author":"Ohtsu","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1634\/theoncologist.10-8-590","article-title":"Targeted Therapies for Esophageal Cancer","volume":"10","author":"Tew","year":"2005","journal-title":"Oncologist"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S1470-2045(13)70096-2","article-title":"Epirubicin, Oxaliplatin, and Capecitabine with or without panitumumab for Patients with Previously Untreated Advanced Oesophagogastric Cancer (REAL3): A Randomised, Open-label Phase 3 Trial","volume":"14","author":"Waddell","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s41588-018-0331-5","article-title":"The landscape of Selection in 551 Esophageal Adenocarcinomas Defines Genomic Biomarkers for the Clinic","volume":"51","author":"Frankell","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.1038\/ncomms6224","article-title":"Genomic Catastrophes Frequently Arise in Esophageal Adenocarcinoma and Drive Tumorigenesis","volume":"5","author":"Nones","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ng.2591","article-title":"Exome and Whole-genome sequencing of Esophageal Adenocarcinoma Identifies Recurrent Driver Events and Mutational Complexity","volume":"45","author":"Dulak","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41586-020-1965-x","article-title":"Analyses of Non-coding Somatic Drivers in 2658 Cancer Whole Genomes","volume":"578","author":"Rheinbay","year":"2020","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1038\/s41467-019-10898-3","article-title":"Patient-specific Cancer Genes Contribute to Recurrently Perturbed Pathways and Establish Therapeutic Vulnerabilities in Esophageal Adenocarcinoma","volume":"10","author":"Mourikis","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hao, D., He, S., Harada, K., Pizzi, M.P., Lu, Y., Guan, P., Chen, L., Wang, R., Zhang, S., and Sewastjanow-Silva, M. (2020). Integrated Genomic Profiling and Modelling for Risk Stratification in Patients with Advanced Oesophagogastric Adenocarcinoma. Gut.","DOI":"10.1136\/gutjnl-2020-322707"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/ng.2760","article-title":"Pan-cancer Patterns of Somatic Copy Number Alteration","volume":"45","author":"Zack","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cell.2011.12.013","article-title":"Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations","volume":"148","author":"Rausch","year":"2012","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Loeser, H., Wolwer, C.B., Alakus, H., Chon, S.H., Zander, T., Buettner, R., Hillmer, A.M., Bruns, C.J., Schroeder, W., and Gebauer, F. (2020). Y Chromosome Loss is a Frequent Event in Barrett\u2019s Adenocarcinoma and Associated with Poor Outcome. Cancers, 12.","DOI":"10.3390\/cancers12071743"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of Mutational Processes in Human Cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The Repertoire of Mutational Signatures in Human Cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/ng.3013","article-title":"Ordering of Mutations in Preinvasive Disease Stages of Esophageal Carcinogenesis","volume":"46","author":"Weaver","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41588-019-0551-3","article-title":"Genomic Evidence Supports a Clonal Diaspora Model for Metastases of Esophageal Adenocarcinoma","volume":"52","author":"Noorani","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch Repair Deficiency Predicts Response of Solid Tumors to PD-1 Blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1038\/s41591-018-0101-z","article-title":"Comprehensive Molecular Characterization of Clinical Responses to PD-1 Inhibition in Metastatic Gastric Cancer","volume":"24","author":"Kim","year":"2018","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/bjs.10663","article-title":"Meta-Analysis of Microsatellite Instability in Relation to Clinicopathological Characteristics and Overall Survival in Gastric Cancer","volume":"105","author":"Polom","year":"2018","journal-title":"Br. J. Surg."},{"key":"ref_29","first-page":"295","article-title":"Epidemiology of Choroidal Folds","volume":"89","author":"Krzykala","year":"1989","journal-title":"Bull. Soc. Ophtalmol. Fr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ejca.2018.02.014","article-title":"Epstein-Barr virus and Mismatch Repair Deficiency Status Differ between Oesophageal and Gastric Cancer: A Large Multi-centre Study","volume":"94","author":"Hewitt","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/1477-3163.120632","article-title":"O-6-methylguanine-deoxyribonucleic Acid Methyltransferase Methylation Enhances Response to Temozolomide Treatment in Esophageal Cancer","volume":"12","author":"Hasina","year":"2013","journal-title":"J. Carcinog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"38","DOI":"10.18632\/genesandcancer.46","article-title":"Methylation of CHFR Sensitizes Esophageal Squamous Cell Cancer to Docetaxel and Paclitaxel","volume":"6","author":"Yun","year":"2015","journal-title":"Genes Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1634\/theoncologist.2018-0143","article-title":"Comparative Molecular Analyses of Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, and Gastric Adenocarcinoma","volume":"23","author":"Salem","year":"2018","journal-title":"Oncologist"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1038\/s41418-021-00745-8","article-title":"Evidence that Polyploidy in Esophageal Adenocarcinoma Originates from Mitotic Slippage Caused by Defective Chromosome Attachments","volume":"28","author":"Scott","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1158\/2159-8290.CD-17-0787","article-title":"Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer","volume":"8","author":"Janjigian","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1677\/erc.1.01047","article-title":"Role of Exon-16-Deleted HER2 in Breast Carcinomas","volume":"13","author":"Castiglioni","year":"2006","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41572-019-0086-z","article-title":"Barrett Oesophagus","volume":"5","author":"Peters","year":"2019","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bpg.2014.11.003","article-title":"The Use of Molecular Markers in Predicting Dysplasia and Guiding Treatment","volume":"29","author":"Zeki","year":"2015","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1001\/jama.287.15.1972","article-title":"Gastroesophageal reflux, barrett esophagus, and esophageal cancer: Scientific review","volume":"287","author":"Shaheen","year":"2002","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"c4551","DOI":"10.1136\/bmj.c4551","article-title":"Diagnosis and Management of Barrett\u2019s Oesophagus","volume":"341","author":"Jankowski","year":"2010","journal-title":"BMJ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1136\/gut.2007.143339","article-title":"Individual Crypt Genetic Heterogeneity and the Origin of Metaplastic Glandular Epithelium in Human Barrett\u2019s Oesophagus","volume":"57","author":"Leedham","year":"2008","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/ng.3357","article-title":"Whole-genome Sequencing Provides New Insights into the Clonal Architecture of Barrett\u2019s Esophagus and Esophageal Adenocarcinoma","volume":"47","author":"Becq","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/ng.3343","article-title":"Paired Exome Analysis of Barrett\u2019s Esophagus and Adenocarcinoma","volume":"47","author":"Stachler","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/s41467-017-02621-x","article-title":"Evolution of Barrett\u2019s Esophagus through Space and Time at Single-crypt and Whole-biopsy Levels","volume":"9","author":"Martinez","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/s41591-020-1033-y","article-title":"Genomic Copy Number Predicts Esophageal Cancer Years before Transformation","volume":"26","author":"Killcoyne","year":"2020","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1053\/j.gastro.2020.01.044","article-title":"Identification of Subtypes of Barrett\u2019s Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data","volume":"158","author":"Jammula","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Guo, X., Tang, Y., and Zhu, W. (2018). Distinct Esophageal Adenocarcinoma Molecular Subtype has Subtype-Specific Gene Expression and Mutation Patterns. BMC. Genom., 19.","DOI":"10.1186\/s12864-018-5165-0"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41418-019-0363-0","article-title":"The MAP3K13-TRIM25-FBXW7alpha Axis Affects c-Myc Protein Stability and Tumor Development","volume":"27","author":"Zhang","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1158\/0008-5472.CAN-17-0267","article-title":"Survival of Head and Neck Cancer Cells Relies upon LZK Kinase-Mediated Stabilization of Mutant p53","volume":"77","author":"Edwards","year":"2017","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"18589","DOI":"10.1038\/s41598-020-75541-4","article-title":"Stromal Microenvironment Promoted Infiltration in Esophageal Adenocarcinoma and Squamous Cell Carcinoma: A multi-cohort gene-based analysis","volume":"10","author":"Li","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e143888","DOI":"10.1172\/jci.insight.143888","article-title":"Immune Determinants of Barrett\u2019s Progression to Esophageal Adenocarcinoma","volume":"6","author":"Lagisetty","year":"2021","journal-title":"JCI. Insight"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.molcel.2015.04.005","article-title":"The Technology and Biology of Single-cell RNA Sequencing","volume":"58","author":"Kolodziejczyk","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41592-019-0654-x","article-title":"Orchestrating Single-cell Analysis with Bioconductor","volume":"17","author":"Amezquita","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the Multicellular Ecosystem of Metastatic Melanoma by Single-Cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e104063","DOI":"10.15252\/embj.2019104063","article-title":"Stromal Cell Diversity Associated with Immune Evasion in Human Triple-negative Breast Cancer","volume":"39","author":"Wu","year":"2020","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1038\/s41467-020-16164-1","article-title":"Single-cell RNA Sequencing Demonstrates the Molecular and Cellular Reprogramming of Metastatic Lung Adenocarcinoma","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/ng.3818","article-title":"Reference Component Analysis of Single-cell Transcriptomes Elucidates Cellular Heterogeneity in Human Colorectal Tumors","volume":"49","author":"Li","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"and Coussens, L.M.; Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/path.4467","article-title":"Cancer-associated Fibroblasts Predict Poor Outcome and Promote Periostin-dependent Invasion in Oesophageal Adenocarcinoma","volume":"235","author":"Underwood","year":"2015","journal-title":"J. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00262-016-1826-5","article-title":"Tumour Infiltrating Lymphocytes Correlate with Improved Survival in Patients with Oesophageal Adenocarcinoma","volume":"65","author":"Noble","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4261","DOI":"10.1038\/s41467-018-06796-9","article-title":"Single Cell RNA-seq Reveals Profound Transcriptional Similarity between Barrett\u2019s Oesophagus and Oesophageal Submucosal Glands","volume":"9","author":"Owen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/1878-0261.12680","article-title":"Cell Type-specific Transcriptomics of Esophageal Adenocarcinoma as a Scalable Alternative for Single Cell Transcriptomics","volume":"14","author":"Kramer","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41467-019-13915-7","article-title":"Extreme Intratumour Heterogeneity and Driver Evolution in Mismatch Repair Deficient Gastro-oesophageal Cancer","volume":"11","author":"Woolston","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-018-1612-0","article-title":"The Network of Cancer Genes (NCG): A Comprehensive Catalogue of Known and Candidate Cancer Genes from Cancer Sequencing Screens","volume":"20","author":"Repana","year":"2019","journal-title":"Genome Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1053\/j.gastro.2017.07.007","article-title":"The Evolving Genomic Landscape of Barrett\u2019s Esophagus and Esophageal Adenocarcinoma","volume":"153","author":"Contino","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMra1314530","article-title":"Esophageal Carcinoma","volume":"371","author":"Rustgi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1056\/NEJMoa1112088","article-title":"Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer","volume":"366","author":"Hulshof","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1093\/annonc\/mdn403","article-title":"Biweekly Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT) for Patients with Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie","volume":"19","author":"Hartmann","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S843","DOI":"10.21037\/jtd.2017.06.123","article-title":"Non Responders to Neoadjuvant Chemoradiation for Esophageal Cancer: Why Better Prediction is Necessary","volume":"9","author":"Smit","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in Combination with Chemotherapy Versus Chemotherapy Alone for Treatment of HER2-positive Advanced Gastric or Gastro-oesophageal Junction Cancer (ToGA): A Phase 3, Open-label, Randomised Controlled Trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1001\/jamaoncol.2018.5441","article-title":"Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study","volume":"5","author":"Shah","year":"2019","journal-title":"JAMA. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S1470-2045(20)30169-8","article-title":"First-line Pembrolizumab and Trastuzumab in HER2-positive Oesophageal, Gastric, or Gastro-oesophageal Junction Cancer: An Open-label, Single-arm, Phase 2 Trial","volume":"21","author":"Janjigian","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1158\/1078-0432.CCR-11-2272","article-title":"Association of HER2\/ErbB2 Expression and Gene Amplification with Pathologic Features and Prognosis in Esophageal Adenocarcinomas","volume":"18","author":"Yoon","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Plum, P.S., Gebauer, F., Kramer, M., Alakus, H., Berlth, F., Chon, S.H., Schiffmann, L., Zander, T., Buttner, R., and Holscher, A.H. (2019). HER2\/neu (ERBB2) expression and Gene Amplification Correlates with Better Survival in Esophageal Adenocarcinoma. BMC. Cancer, 19.","DOI":"10.1186\/s12885-018-5242-4"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/jso.20070","article-title":"Vascular Endothelial Growth Factor in Esophageal Cancer","volume":"87","author":"Kleespies","year":"2004","journal-title":"J. Surg. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(13)61719-5","article-title":"Ramucirumab Monotherapy for Previously Treated Advanced Gastric or gastro-Oesophageal Junction Adenocarcinoma (REGARD): An international, Randomised, Multicentre, Placebo-Controlled, Phase 3 Trial","volume":"383","author":"Fuchs","year":"2014","journal-title":"Lancet"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/S1470-2045(14)70420-6","article-title":"Ramucirumab Plus Paclitaxel Versus Placebo Plus Paclitaxel in Patients with Previously Treated Advanced Gastric or Gastro-oesophageal Junction Adenocarcinoma (RAINBOW): A Double-blind, Randomised Phase 3 Trial","volume":"15","author":"Wilke","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S1470-2045(18)30791-5","article-title":"Ramucirumab with Cisplatin and Fluoropyrimidine as First-line Therapy in Patients with Metastatic Gastric or Junctional Adenocarcinoma (RAINFALL): A Double-blind, Randomised, Placebo-controlled, Phase 3 Trial","volume":"20","author":"Fuchs","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1002\/1878-0261.12907","article-title":"Molecular Profiles of Response to Neoadjuvant Chemoradiotherapy in Oesophageal Cancers to Develop Personalized Treatment Strategies","volume":"15","author":"Goedegebuure","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_81","first-page":"150","article-title":"Burned adolescents\u2019 descriptions of their coping strategies","volume":"17","author":"Sutherland","year":"1988","journal-title":"Heart Lung"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/bjc.2016.219","article-title":"Genetic Progression of Barrett\u2019s Oesophagus to Oesophageal Adenocarcinoma","volume":"115","author":"Gregson","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/j.gastro.2018.03.047","article-title":"Detection of Mutations in Barrett\u2019s Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma","volume":"155","author":"Stachler","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41467-017-02584-z","article-title":"Elucidating the Genomic Architecture of Asian EGFR-Mutant Lung Adenocarcinoma through Multi-region Exome Sequencing","volume":"9","author":"Nahar","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S1470-2045(16)30240-6","article-title":"Genome-wide Association Studies in Oesophageal Adenocarcinoma and Barrett\u2019s Oesophagus: A Large-scale Meta-analysis","volume":"17","author":"Gharahkhani","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_86","unstructured":"SERVIER, L.L. (2021, June 29). Servier Medical Art. Available online: https:\/\/smart.servier.com."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:52:25Z","timestamp":1760165545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,26]]},"references-count":86,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cancers13174300"],"URL":"https:\/\/doi.org\/10.3390\/cancers13174300","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,26]]}}}