EGAGenomicsIllumina HiSeq 2500;https://ega-archive.org/datasets/EGAD0000100136447EGA dataset EGAD00001001364EGA<h4>Unlabelled</h4>Esophageal adenocarcinomas are associated with a dismal prognosis. Deciphering the evolutionary history of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable esophageal adenocarcinomas, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of esophageal adenocarcinomas with the presence of heterogeneous driver mutations, parallel evolution, early genome-doubling events, and an association between high intratumor heterogeneity and poor response to NAC. Multiregion sequencing demonstrated a significant reduction in thymine to guanine mutations within a CpTpT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of cytosine to adenine mutations within a CpC context following NAC. Esophageal adenocarcinomas are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches.<h4>Significance</h4>This work illustrates dynamic mutational processes occurring during esophageal adenocarcinoma evolution and following selective pressures of platinum exposure, emphasizing the iatrogenic impact of therapy on cancer evolution. Identification of amplifications encoding targetable oncogenes maintained through NAC suggests the presence of stable vulnerabilities, unimpeded by cytotoxics, suitable for therapeutic intervention.Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy.Murugaesu Nirupa N, Wilson Gareth A GA, Birkbak Nicolai J NJ, Watkins Thomas T, McGranahan Nicholas N, Kumar Sacheen S, Abbassi-Ghadi Nima N, Salm Max M, Mitter Richard R, Horswell Stuart S, Rowan Andrew A, Phillimore Benjamin B, Biggs Jennifer J, Begum Sharmin S, Matthews Nik N, Hochhauser Daniel D, Hanna George B GB, Swanton Charles CDrug, Therapy, oesophageal adenocarcinoma, EAC, esophagus adenocarcinoma, oesophagus adenocarcinoma, Pharmacotherapy, adenocarcinoma of oesophagus, chemotherapy, Therapies, Chemotherapies., Chemotherapy, adenocarcinoma of the oesophagus, esophageal adenocarcinoma, pharmacologic therapy, pharmacotherapy, Pharmacotherapies, adenocarcinoma of the esophagus, Drug Therapies, adenocarcinoma - esophagus, adenocarcinoma of esophagus, adenocarcinoma - oesophagusVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASPNalp1, Amenable, Adenomas, SLEV1, Parallel Lesion, Visible Light, mercapturic acid, Tumor, ADNOS, Mutations, sequencing assay, Associations, Granular Cell Adenocarcinoma, parallel design trial, 2, Tubular Carcinoma, Decreased, 4, Chromosomal Stabilities, domain, Contains, Fs(3)Hor, Cribriform Carcinoma, imprinted and ancient gene protein, A, treatment, C, G, Genomes, Adenoma, INTRATUMOR, Reduced, coding, T, 4-amino-2(1H)-pyrimidinone, Evolution, NTef2, {EVENTS}, Poor, Malignant Germ Cell International Collaborative Risk Classification, Thy, Application Context, Transforming Genes, Homo sapiens disease, XKR1, Protein Domain, adenocarcinoma of esophagus, CLR17.1, Tumors, Protein Feature, close to, Ade, Radiation, anatomical protrusion, Followed By, sequencing_assay, alpha-NAC, Array Feature, UNQ391/PRO726, Doubling, Low Income, Light, 6H-Purin-6-one, Procedure, historical aspects, Fs(3)Sz11, MaGIC Risk, DmelCG8759, Signed, LIGHT, Benign, alphaNAC, Chromosome Instability, Encoding, Chemotherapy, X1k, (2R)-2-acetylamino-3-sulfanylpropanoic acid, Carcinomas, Enrichment, statistical significance, platine, HVEML, platino, IMDC Poor Risk Group, chromosomal passenger complex, adenocarcinoma of oesophagus, induction therapy, Benign Neoplasms, 5-methyluracil, whole genome, Neoadjuvant Therapy, MCLDS, adenocarcinoma of the esophagus, Rationale, 78Pt, Genomic, Malignant Neoplasms, Leading, Poor CALGB Criteria, Characterized, Oncogene, oesophageal adenocarcinoma, CARD7, Chromosome, Imaging Feature, historical notes, 2-amino-1, CG2684, NAC, NALP1, adenocarcinoma of the oesophagus, Cytosin, other neoplasm, E430016J11Rik, Adenocarcinoma, whole exome, Aspect, chemotherapy, Neoplasms, number, Vitamin B 4, Gua, Esophageal, Prognostic Factors, l(2)04329, adenocarcinoma - oesophagus, Granular Cell Adenocarcinomas, Ly113, Enrich, Biopolymer Sequencing, disease or disorder, Projections and Predictions, aic, Chromosomal Instabilities, Drug Therapies, Chromosome Stabilities, Transforming Gene, interventionDescription, Tubular Adenocarcinoma, Events, CpC, 3H)-dione, STABLE, Sequencing, cytidine-3'-phosphate-5'-cytidine, L-acetylcysteine, Neoplasias, Platinum Black, Granular Cell Carcinomas, N-acetyl-L-(+)-cysteine, SURGICAL AND MEDICAL PROCEDURES., (R)-2-acetylamino-3-mercaptopropanoic acid, Statistically Significant, KX, genome, I-TUMOR, TR2, NACA, CPC, Cancer, CPC complex, Nalp1a, VAMAS1, Gm14, Malignant Neoplasm, MSI stable, Gm15, Basal Cell, Preceding, disorders, Factor, CD258, parallel group trial, Chromosomal, near to, MT, DEFCAP-L|S, Double, Neoplasm, condition, imprinted and ancient gene protein homolog, IMPACT, NA, Granular Cell, Before, Intervention, primary cancer, Intratumor Route of Administration, parallel trial, HVEM-L, Encode, Containing, Cancers, Lds, malignant tumor, Malignant Adenomas, Protein Region, 5-methyl-, Photoradiations, vicinity of, Instability, Neoplasia, Feature, N-acetylcysteine, CG8759, Characterization, Significant, Platin, Induction Therapy, DEFCAP-L/S, Driver Device, 5-Methyluracil, Pt, diseases, 4-dihydroxy-5-methylpyrimidine, Statistical Significance, diseases and disorders, Transforming, Prior, IMDC Poor, KIAA0926, Chromosome Instabilities, Protein Motif, human disease, DmelCG2684, Prognoses, esophagus adenocarcinoma, 5-methyl-2, Identification, statistically significant, Granular Cell Carcinoma, 1H-Purin-6-amine, Futurology, Tubular Carcinomas, Histories, Comprise, 7-dihydro-, DEFCAP, 5 Methyluracil, Context, Chromosomal Stability, TNFSF14, malignant neoplasm, Subsequent, CDISC Events Class, 3H)-Pyrimidinedione, CIDED, disease management, Therapies, Event Unit, Malignancies, Intratumor, Zytosin, PARALLEL, Predictions and Projections, Therapy, NACalpha, operable, Pre, Carcinoma, Thymin, 4-amino-, Adenocarcinomas, Parallel Study, Significance, DECREASED, 2-Amino-6-hydroxypurine, Cyt, Contained, Poverty, Tubular, Malignant Adenoma, significant, neoadjuvant therapy, Diseases, NOS, Decrease, esophageal adenocarcinoma, Region, Basal Cell Adenocarcinoma, Preoperative Therapy, Domain, Visible Radiations, 2(1H)-Pyrimidinone, Visible Radiation, Image Feature, Factors, Vitamin, Pharmacotherapy, Neoadjuvant, Driver, Nucleic Acid Sequencing, Adenin, Operable, Prognostic, MSI Stable, Heterogeneity, Exomes, Cribriform, 3H)-pyrimidinedione, Features, Treatments, Tubular Adenocarcinomas, early, Identified, disease, Patient, spine, Horka, acetilcisteina, Suitable, Fs(3)Horka, IMDC Poor Risk, Sequence Analysis, Prognostic Factor, other disease, 5-methylpyrimidine-2, Material Identification, Oxyphilic Adenocarcinoma, Benign Neoplasm, Gene, pharmacotherapy, Vitamin B, Pharmacotherapies, Malignant, Ximpact, presence, Chemotherapies, protrusion, Intervention or Procedure, Stability, SEQUENCING, EAC, Instabilities, Genetic heterogeneity, DmF2, Basal Cell Adenocarcinomas, Next, Intratumoral Route of Administration, lod, Routine Signature, Parallel Trial, oesophagus adenocarcinoma, Malignancy, Reduction, Interventional, Visible, Cribriform Carcinomas, Contain, non-neoplastic, Following, Nlrp1, Stable, Clients, MSS, heterogeneity, disorder, Characteristics, adenocarcinoma - esophagus, Intervention Strategies, Oxyphilic, EVENTS, Molecular Biology, Encoded, Acetylcysteine, Parallel, medical condition, Chromosome Stability, Historical Aspects, Microsatellite Stable, Historical Aspect, Client, impact-a, Stabilities, L-alpha-acetamido-beta-mercaptopropionic acid, count in organism, 6-Aminopurine, Characteristic, 2-amino-6-oxopurine, 4(1H, Oxyphilic Adenocarcinomas, signatureText, Radiations, esophageal, Genes, Intratumoral use, Reason, Photoradiation, B 4, PP1044, LTg, NUCLEIC ACID SEQUENCING, Drug, 4-amino-2-hydroxypyrimidine, Pressures, Therapeutic, (R)-mercapturic acid, approaches, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Criteria - Poor-Risk Group, BEFORE, Treatment, pharmacologic therapy, acetylcysteinum, Aspects, Signature, Future, Genome, RWDD5, Historical, Motifaverage, whole exome, esophagus adenocarcinoma, oesophagus adenocarcinoma, Malignant Neoplasm, Data Set, whole blood, Malignancy, adenocarcinoma of oesophagus, Neoplasms, Benign Neoplasm, Benign Neoplasms, Cancers, adenocarcinoma of the esophagus, Tumor, Malignant, HiSeq 2500, adenocarcinoma - oesophagus, Malignant Neoplasms, Neoplasias, oesophageal adenocarcinoma, EAC, Benign, Neoplasm, adenocarcinoma of the oesophagus, esophageal adenocarcinoma, Malignancies, median., other neoplasm, adenocarcinoma - esophagus, Neoplasia, adenocarcinoma of esophagus, Cancer, Tumorsfalseena-DATASET-UCL-14-05-2015-18:11:37:007-120 - samplesThis dataset contains whole exome data from 8 esophageal adenocarcinoma tumors, that has been subjected to multiregion sequencing, ranging from 3-8 regions per tumor. In total, 40 tumor samples and 8 normal blood samples have been sequenced on Illumina HiSeq 2500 at a median dept of 90x.2017-07-26 15:39:26EGAD00001001364960626003801EGAC00001000340EGAS00001001254