EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD0000100339560EGA dataset EGAD00001003395EGA<h4>Purpose</h4>Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) is fatal in 90% of patients, and yet little is known about its biology.<h4>Experimental design</h4>Using exome sequencing, we characterized the mutation profiles of 38 rrDLBCL biopsies obtained at the time of progression after immunochemotherapy. To identify genes that may be associated with relapse, we compared the mutation frequency in samples obtained at relapse to an unrelated cohort of 138 diagnostic DLBCLs and separately amplified specific mutations in their matched diagnostic samples to identify clonal expansions.<h4>Results</h4>On the basis of a higher frequency at relapse and evidence for clonal selection, TP53, FOXO1, MLL3 (KMT2C), CCND3, NFKBIZ, and STAT6 emerged as top candidate genes implicated in therapeutic resistance. We observed individual examples of clonal expansions affecting genes whose mutations had not been previously associated with DLBCL including two regulators of NF-κB: NFKBIE and NFKBIZ We detected mutations that may be affect sensitivity to novel therapeutics, such as MYD88 and CD79B mutations, in 31% and 23% of patients with activated B-cell-type of rrDLBCL, respectively. We also identified recurrent STAT6 mutations affecting D419 in 36% of patients with the germinal center B (GCB) cell rrDLBCL. These were associated with activated JAK/STAT signaling, increased phospho-STAT6 protein expression and increased expression of STAT6 target genes.<h4>Conclusions</h4>This work improves our understanding of therapeutic resistance in rrDLBCL and has identified novel therapeutic opportunities especially for the high-risk patients with GCB-type rrDLBCL. Clin Cancer Res; 22(9); 2290-300. ©2015 AACR.Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas.Morin Ryan D RD, Assouline Sarit S, Alcaide Miguel M, Mohajeri Arezoo A, Johnston Rebecca L RL, Chong Lauren L, Grewal Jasleen J, Yu Stephen S, Fornika Daniel D, Bushell Kevin K, Nielsen Torsten Holm TH, Petrogiannis-Haliotis Tina T, Crump Michael M, Tosikyan Axel A, Grande Bruno M BM, MacDonald David D, Rousseau Caroline C, Bayat Maryam M, Sesques Pierre P, Froment Remi R, Albuquerque Marco M, Monczak Yury Y, Oros Kathleen Klein KK, Greenwood Celia C, Riazalhosseini Yasser Y, Arseneault Madeleine M, Camlioglu Errol E, Constantin André A, Pan-Hammarstrom Qiang Q, Peng Roujun R, Mann Koren K KK, Johnson Nathalie A NAVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASPDLBCL, WES, Complete Transcriptome, thymus nucleic acid, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Complete Exome Sequencings, DNS, Data Set, (Deoxyribonucleotide)n, Complete Exome, Complete Exome Sequencing, DNAn+1, Whole Transcriptome Sequencing, Exome, Double Stranded, Deoxyribonucleic acid, Double-Stranded, Sequencing, Deoxyribonucleic acids, (Deoxyribonucleotide)n+m, Exome Sequencing, Whole Exome, Deoxyribonucleic Acid, Whole, ds DNA, Whole Exome Sequencing, Desoxyribonukleinsaeure, Whole Transcriptome, Transcriptome Sequencing, Double-Stranded DNA, (Deoxyribonucleotide)m, DNA, deoxyribonucleic acids, DNAn, ds-DNA, diffuse large B-cell lymphoma., other neoplasm, desoxyribose nucleic acid, Transcriptome SequencingsB Cells, diffuse, gyltl1b-b, B Lymphocytes, acetylglucosaminyltransferase-like protein, Bursa-Dependent Lymphocytes, familial, B cell, Mbp1, Germinoblastoma, Malignant, Germinoblastic Sarcoma, Reticulolymphosarcoma., LARGE1, froggy, Gyltl1a, Malignant Lymphomas, Reticulolymphosarcomas, MDDGA6, mKIAA0609, Germinoblastic Sarcomas, Germinoblastic, KIAA0609, myd, Lymphomas, acetylglucosaminyltransferase-like 1A, fg, Sarcomas, B-cell, gyltl1b, like-acetylglucosaminyltransferase, MDDGB6, scattered, mdc1d, Mbp-1, Bursa-Equivalent Lymphocyte, LARGE, Germinoblastomas, LARGE_HUMAN, genetic, BPFD#36, MDC1D, Malignant Lymphoma, Sarcoma, like-glycosyltransferase, enr, B lymphocyte, B-Lymphocyte, Lymphoma, inherited genetic, B-lymphocyte, constitutitional genetic, hereditary, glycosyltransferase-like protein LARGE1Experimental Designs, UVO Gene Mutation, Ghrfr, B Cells, Materials, Disorders, H. pylori Positive, Adjustments, dMyD88, B cell, Myd88F, A4, Tumor, ERBB2 Amplification, HALR, Positive Charge, dmTAF[[II]]230, RET/PTC Rearrangement, Hepatitis C Virus RNA Positive, p53 Mutation, PGR Positive, dMyd88, Whole Transcriptome, Transcriptome Sequencing, 5, Activate, Unrelated to Intervention, gamma sarcoglycan, Methylated MGMT Promoter, FOXO1A, ERA Positive, G Protein Subunit Alpha q Gene Mutation, Germinal, cel, IDH Gene Mutation, CD324 Gene Mutation, Moods, Hepatitis B Virus Core Antibody Positive, c-KIT Positive, Flavoprotein Subunit of Complex II Positive, B7H1 Positive, BEK Gene Mutation, node-positive, Cadherin 1 Gene Mutation, ESTRB Positive, Based, XH2 Gene Mutation, Center, Catenin Beta 1 Gene Mutation, ER Beta Positive, Telomerase Reverse Transcriptase Gene Promoter Mutation, AESDTH, Data Reporting, Methylated MGMT Gene Promoter, Tumors, Clonality, screening, dTAF[[II]]230, Human Immunodeficiency Virus Positive, KGFR Gene Rearrangement, Research Methodology, c-erbB2 Gene Amplification, Fkhr, AACR, Longterm Effect, B-RAF Gene Rearrangement, Observation Result, Anti-HBc Positive, Hepatitis B Virus Surface Antibody Positive, Estrogen Receptor Alpha Positive, Experimental, Benign, SDHIP Positive, Tumor Progression, Disease Progression, Relative Risks, About, Obtain, Technics, Dx, FGFR-2 Gene Rearrangement, Problem Formulation, FLT2 Gene Mutation, FGFR-1 Gene Rearrangement, RET Gene Rearrangement, Complete Transcriptome, NRAS Gene Mutation, IKBE, Non-Neoplastic, c-erbB1 Gene Amplification, Cancer Disease Progression, ECAD Gene Mutation, Benign Neoplasms, IKBZ, EST2 Promoter Mutation, surveillance, Present, ESR Positive, PDCD1L1 Positive, Malignant Neoplasms, Formulations, LD20892, DmelCG2078, Positive EBV Serum Test, IDH Gene Family Mutation, Taf250, B-Lymphocyte, 35kD dystrophin-associated glycoprotein, GR, Fatal, Diseases and Disorders, Whole Exome Sequencing, N-RAS Gene Mutation, HER2/Neu Amplification, KRAS Gene Mutation, Detected, clone, Expression of PD-L1, Previous, SDHF Positive, Nuclear Receptor Subfamily 3 Group A Member 2 Positive, BRCA1-Associated Protein 1 Gene Mutation, CDHE Gene Mutation, Neoplasms, Succinate Dehydrogenase [Ubiquinone] Iron-Sulfur Subunit, Hepatitis B Virus Surface Antigen Positive, KIAA1506, Unrelated, Sources, MAM, G Protein Subunit Alpha 11 Gene Mutation, Technique, B7-H Positive, DLBCL, Cadherin-Associated Protein, Exome Sequencings, dTAF[[II]]250, MGMT Gene Methylation, Longterm, disease progression, Recrudescences, cell, Hepatitis B Core Antibody Positive, prevalence, Target, Former, Sequencing, Research Strategy, BEK Gene Rearrangement, Neoplasias, dTAF250, RET Rearrangement, RAD54 Homolog Gene Mutation, Monotypic Cell Population Present, Fkhr1, HER-2 Gene Amplification, Including, Amplified, MYD88, New, Positive EBV Test, findings, Complete Exome Sequencings, Malignant Neoplasm, Affects, PR Positive, Hepatitis B Surface Protein Antigen Positive, DmMyd88, Estrogen Receptor Positive, RGD1310834, EGFR Amplification, dTAF230, Research Strategies, GREECE, B-RAF1 Gene Rearrangement, ATRX, MT, BRAF Gene Rearrangement, Long Term Effects, condition, FLG Gene Mutation, PAX8 Rearrangement, Androgen Receptor Positive, activate, HGFR Gene Amplification, ESR1 Positive, MET Gene Amplification, c-MET Gene Amplification, Relative Risk, Taf[[II]]250, ER-Alpha Positive, Methylated MGMT, progression, JAK/STAT, ERG Rearrangement, Research Designs, HBsAg Positive, American Association of Cancer Research., Bursa-Equivalent Lymphocyte, Understanding, malignant tumor, TERT Gene Promoter Mutation, High, Data Adjustment, Grade 5, Ret Proto-Oncogene Rearrangement, At Relapse, Monotypic, signalling process, Afxh, Specific, IDH Mutation, 1p/19q Co-deletion, target lesion, SDHA Positive, Mail, Q Polypeptide Gene Mutation, disease_term, Strategy, Succinate Dehydrogenase [Ubiquinone] Flavoprotein Subunit, Neoplasia, Estrogen Receptor 2 Positive, XNP Gene Mutation, O-6-Methylguanine-DNA Methyltransferase Gene Promoter Methylation, IL-4-STAT, Approximate, ER Positive, Bursa-Dependent Lymphocytes, v-Ets Erythroblastosis Virus E26 Oncogene Like Gene Rearrangement, selection process, Characterization, Activated, Technic, Tp53, protein expression, HRAS1 Gene Mutation, G-ALPHA-q Gene Mutation, BAP1 Gene Mutation, Techniques, Readability, Clonal, Relapses, Foxo1a, v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 Gene Mutation, Detection, TP53, Abnormal, gene expression, STAT6B, Group, STAT6C, increased, Estrogen Receptor Beta Positive, Identification, Common Terminology Criteria for Adverse Events Grade 5, diffuse large B-cell lymphoma, Whole Transcriptome Sequencing, Recurrences, DOG1 Positive, Groups, CG2078, ETV Family Gene Rearrangement, Ets Variant Family Rearrangement, EGFR Gene Amplification, FLT2 Gene Rearrangement, Rearrangement identified, Novel, FGFR3 Gene Rearrangement, ECT1 Gene Mutation, Estrogen Receptor 1 Positive, B lymphocyte, Fibroblast Growth Factor Receptor 2 Gene Mutation, Other Disease, IDH Family Mutation, CD333 Gene Rearrangement, Research Techniques, DmMyD88, FoxO1A, Long-Term Effects, ATRX Gene Mutation, ERG Gene Rearrangement, Relapse, Janus Kinase/Signal Transducer and Activator of Transcription, lit, HER2 Gene Mutation, TAFII-250, TAF250/230, results, Gene Expression, TAFII250, lymhpoid nodule, Hepatitis B Surface Antibody Positive, HIV Positive, lymph node nodule, Problem, HIV positive, FoxO1, 1p/19q Codeletion, POSITIVE, Guanine Nucleotide Binding Protein (G Protein), Yes, SDH2 Positive, ERBB2 Gene Mutation, CG17603, TAF[[II]], Treatments, disease, IGB, DMDA, GCB, Specificity and Sensitivity, Expressed, Purpose, ER-Beta Positive, P53, p44, HRAS Gene Mutation, Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation, BRAF Rearrangement, CDH1 Gene Mutation, SGCG_HUMAN, p53, Greece, clonality, Anti-HBs Positive, dTAFII250, c-erbB2 Gene Activation, Malignant, supernumerary, dmTAF1, Fp Positive, Scoring Methods, Fibroblast Growth Factor Receptor 1 Gene Rearrangement, OGD Gene Mutation, Anti-HBcAb Positive, Hep C RNA Positive, CD274 Antigen Positive, Epithelial Gene Mutation, TAF250, MET Proto-Oncogene, Scoring, Research, DIAG, SWS Gene Mutation, TAOS2 Positive, Methylguanine-DNA Methyltransferase Gene Promoter Methylation, Neuroblastoma RAS Viral Oncogene Homolog Gene Mutation, H-ras Gene Mutation, ETV Gene Rearrangement, Clients, Disorder, Error Source, CD332 Gene Rearrangement, Ets Variant Gene Family Rearrangement, disorder, Sensitivity, HER2 Gene Amplification, Long-Term Effect, TRP53, Strategies, TAF, Death Related to Adverse Event, CTNNB Gene Mutation, progesterone receptor positive, RASH1 Gene Mutation, incidence, Epidermal Growth Factor Receptor Gene Activation, TAF[[II]]250, target_lesion, Anti-Hepatitis B Virus Core Antibody Positive, Targeted, l(3)84Ab, Xp53, NR3A2 Positive, Germinal Centers, p230, MGMT Gene Promoter Methylation, TMEM16A Positive, Catenin Beta-1 Gene Mutation, MGMT Methylation, AR Positive, Complete Transcriptome Sequencing, TAF[[II]]230, FMS-Like Tyrosine Kinase 2 Gene Mutation, HIV Positivity, Candidate Gene, Mast/Stem Cell Growth Factor Receptor Kit Positive, Risks, FGFR-2 Gene Mutation, Target Gene, Calcium-Dependent Adhesion Protein, present in greater numbers in organism, DmelCG17603, Therapeutic, Data, SCARMD2, Treatment, HBs Antigen Positive, CD274 Molecule Positive, TAF1, GTPase Gene Mutation, Anti-HBsAb Positive, Beta Gene Mutation, Date of Diagnosis, Design, Error Sources, Progesterone Receptor Positive, Diagnosis, FGFBR Gene Rearrangement, Long Term, Mutations, Relative, Compared, Method, bbl, symptoms, Diffuse Large B-Cell Lymphoma Refractory, Nuclear Receptor Subfamily 3 Group A Member 1 Positive, INAP, Erg-3 Gene Rearrangement, CD332 Gene Mutation, Monoclonal Cellular Population Present, Ha-ras Gene Mutation, Progression, Centers, AA408868, EXPRESSED, HRas Proto-Oncogene, Biopsies, TFIID TAF250, BCC7, TRT Promoter Mutation, FKH1, Matched Group, Matched, GAQ Gene Mutation, Met Proto-Oncogene (Hepatocyte Growth Factor Receptor) Gene Amplification, Comparison, FGFR1 Gene Rearrangement, PD-L1+, NEU Gene Mutation, allergic reaction, v-raf Murine Sarcoma Viral Oncogene Homolog B1 Gene Rearrangement, Monotypic Cells Present, FGFR3 Gene Mutation, SDHB Positive, Familiar, Reporting, K-RAS Mutation, CD331 Gene Rearrangement, C-HA-RAS1 Gene Mutation, HER1 Gene Amplification, MET Amplification, ZNF-HX Gene Mutation, Adverse Event Unrelated to Intervention, single organism signaling, ERBB2 Gene Amplification, Beta Catenin Gene Mutation, RES, Index, Research Technic, B Lymphocytes, Diagnosed, MyD88, Exome, TAF200, Clonal Cellular Population Present, Research Proposal, Alpha 11 Gene Mutation, disease_type, CD331 Gene Mutation, ERB Positive, Recrudescence, Cadherin, FKHR, JKT4 Gene Rearrangement, lymph node central zone, sarcoglycan, bfy, Epidermal Growth Factor Receptor Gene Amplification, GRC, CMC1 Gene Mutation, little, P53 Gene Mutation, Guanine Nucleotide-Binding Protein, PAX8 Gene Rearrangement, NR3A1 Positive, signs, Keratinocyte Growth Factor Receptor Gene Rearrangement, HER2 Amplification, CD333 Gene Mutation, Characterized, Positive Epstein-Barr Virus Test, Material, FGFBR Gene Mutation, TCS1 Promoter Mutation, bhy, Data Adjustments, TAF230, BFGFR Gene Mutation, Effects, nodule, Amplification Positive, Matched Groups, HCV RNA Positive, LFS1, ER+, Receptor Tyrosine Kinase Gene Amplification, Adjustment, FGFR1 Gene Mutation, p55 Gene Rearrangement, FLG Gene Rearrangement, sensitive, PDCD1LG1 Positive, gamma-SG, Higher, XMyD88, ETV Rearrangement, androgen receptor positive, HBs Positive, Complete, Diagnostic, Activation, occurrence, Positive Number, positive test result, v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Gene Mutation, Long-Term, GNAQ Gene Mutation, PD-L1 Positive, CTNNB1 Gene Mutation, Whole Exome, FGFR2 Gene Rearrangement, ANO1 Positive, Whole, RAD54 Gene Mutation, 300, Approximately, Expression, Cancer, Jak-STAT signaling pathway, CD117 Positive, FGFR2 Gene Mutation, Slc35b2, Helicobacter pylori Positive, 35 kDa dystrophin-associated glycoprotein, ESRB Positive, Matching, MAIL, BG:DS00004.13, Cell, SGCG, Positive Finding, Exome Sequencing, diagnosis, GNA11 Gene Mutation, Standard Toxicity Grade 5, Neoplasm, TAF[[II]]250/230, Hepatocyte Growth Factor Receptor Gene Amplification, outbreaks, Destination, Candidate Genes, primary cancer, DMDA1, HBcAb Positive, EP(2)2535, increased number, Match, disease term, Candidate Disease Gene, Tumor Protein p53 Gene Mutation, Specificity, Upon Relapse, Research Technics, IP Positive, Cancers, Hepatitis B Surface Antigen Positive, C78795, Longterm Effects, N-RAS Mutation, FLT-2 Gene Mutation, ETS Transcription Factor ERG Gene Rearrangement, Error, CEK Gene Mutation, epidemics, Alpha-11 Gene Mutation, Chromatin Remodeler Gene Mutation, lymph node activated zone, MGC130048, Research Technique, Previously, Problem Formulations, Fibroblast Growth Factor Receptor 1 Gene Mutation, B29, GBA1, Hepatitis C Viral RNA Positive, GLUC, FLT-2 Gene Rearrangement, JKT4 Gene Mutation, CTCAE Grade 5, AR+, Highly, KRAS Mutation, disease type, AL024085, Refractory Diffuse Large B-Cell Lymphoma, relapse, ESR-Beta Positive, Fibroblast Growth Factor Receptor 2 Gene Rearrangement, FGFR-3 Gene Rearrangement, D12S1644, KGFR Gene Mutation, Effect, Obtained, Experimental Design, estrogen receptor positive, Targeting, MYD88D, Protein Expression, Observed, Complete Exome Sequencing, Designs, Alpha Thalassemia/Mental Retardation Syndrome X-Linked Gene Mutation, experimental design, c-Met Gene Amplification, PR+, FMS-Like Tyrosine Kinase 2 Gene Rearrangement, malignant neoplasm, Anti-Hepatitis B Core Antibody Positive, Therapies, B7 Homolog 1 Positive, gamma-sarcoglycan, Beta 1 (88kD) Gene Mutation, Malignancies, Positive, 9230106B05Rik, TARGET, Therapy, AW146355, Anti-HBs Antibody Positive, TP53 Gene Mutation, frequency, SG-gamma, Research Proposals, 1p/19q co-deletion, KIT Proto-Oncogene Tyrosine Protein Kinase Positive, v-Ha-ras Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation, Positive Estrogen Receptor, HBsAb Positive, K-SAM Gene Mutation, Succinate Dehydrogenase Complex Flavoprotein Subunit A Positive, Diseases, Genetic Materials, Succinate Dehydrogenase Complex Iron Sulfur Subunit B Positive, Amplification Detected, Genetic Material, KRAS2 Gene Mutation, Paired Domain Gene 8 Gene Rearrangement, Risk, AA682053, Programmed Cell Death 1 Ligand 1 Positive, ESR2 Positive, gamma (35kDa dystrophin-associated glycoprotein), Hepatitis C RNA Positive, morbidity, DMMYD88, Clone, Type 1, Identified, Positive Laboratory Test Result, Paired Box 8 Gene Rearrangement, LCAM Gene Mutation, Patient, SR3-5, E-Cadherin Gene Mutation, Cistron, Arc-1 Gene Mutation, Transcriptome Sequencings, myd88d, N-SAM Gene Mutation, N-SAM Gene Rearrangement, accessory, CD274 Positive, myd88, d230, Complete Exome, KRAS-2 Gene Mutation, PDL1 Positive, Benign Neoplasm, Gene, KIT Positive, Scoring Method, Anti-HBc Antibody Positive, Compare, TERT Promoter Mutation, EfW1, KAL2 Gene Mutation, FATAL, TYPE, ECT1 Gene Rearrangement, DAGA4, Anoctamin-1 Positive, FGFR-3 Gene Mutation, Taf230, resistance, 35DAG, Anti-Hepatitis B Virus Surface Antibody Positive, Mood, SCG3, HIV test positive, sensitivity, Erb-B2 Receptor Tyrosine Kinase Gene Mutation, BFGFR Gene Rearrangement, Methodology, WES, Taf200, B-cell, Genetic, Malignancy, Proposals, Fibroblast Growth Factor Receptor 3 Gene Mutation, Cadherin 1, E-Cadherin (Epithelial) Gene Mutation, HER2/neu Gene Mutation, Taf1p, BRCA1 Associated Protein 1 Gene Mutation, v-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Positive, Unrelated Attribution, MLL3, Trp53, Positive Lymph Node, C-H-RAS Gene Mutation, OGD Gene Rearrangement, Known, KAL2 Gene Rearrangement, SDH1 Positive, ER Alpha Positive, date of diagnosis, UCHL2 Gene Mutation, RAD54L Gene Mutation, FORMER, Disease, GNA-11 Gene Mutation, AI876417, Target Lesion Identification, CEK Gene Rearrangement, date_of_diagnosis, Formulation, Gene Amplification Positive, Cistrons, Loss of Chromosomes 1p/19q, Client, ESTRR Positive, K-SAM Gene Rearrangement, LGMD2C, DIAGNOSIS, del(1p/19q), Fibroblast Growth Factor Receptor 3 Gene Rearrangement, Disease or Disorder, TFIID, ESRA Positive, Kra, Proposal, Methods, ERBB2 Mutation, Basic, ETV Family Rearrangement, purpose, Beta-Catenin Gene Mutation, GA11 Gene Mutation, Paired Box Gene 8 Gene Rearrangement, TP2 Promoter Mutation, Source, Grade 5 Death Related to Adverse Event, Basis, ORAOV2 Positive, TAF[II]250, kra, endemics, Jak-STAT Signaling Pathway, Specified, BAP1 Mutation, c-K-ras Gene Mutation, Cancer Progression, FGFR-1 Gene Mutation, Inclusive, EGFR Gene Activation, B-lymphocyte, Mitochondrial Positivefalseena-DATASET-SFU-20-06-2017-22:32:50:620-88 - samplesThis dataset consists of the exome sequencing data for 30 tumour and germline DNA pairs derived from relapsed/refractory DLBCL.2022-11-22 12:10:03EGAD00001003395960626647218EGAC00000000011EGAS00001001553