EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD0000100107492EGA dataset EGAD00001001074EGA<h4>Background</h4>Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, with 30% to 40% of patients failing to be cured with available primary therapy. microRNAs (miRNAs) are RNA molecules that attenuate expression of their mRNA targets. To characterize the DLBCL miRNome, we sequenced miRNAs from 92 DLBCL and 15 benign centroblast fresh frozen samples and from 140 DLBCL formalin-fixed, paraffin-embedded tissue samples for validation.<h4>Results</h4>We identify known and candidate novel miRNAs, 25 of which are associated with survival independently of cell-of-origin and International Prognostic Index scores, which are established indicators of outcome. Of these 25 miRNAs, six miRNAs are significantly associated with survival in our validation cohort. Abundant expression of miR-28-5p, miR-214-5p, miR-339-3p, and miR-5586-5p is associated with superior outcome, while abundant expression of miR-324-5p and NOVELM00203M is associated with inferior outcome. Comparison of DLBCL miRNA-seq expression profiles with those from other cancer types identifies miRNAs that were more abundant in B-cell contexts. Unsupervised clustering of miRNAs identifies two clusters of patients that have distinct differences in their outcomes. Our integrative miRNA and mRNA expression analyses reveal that miRNAs increased in abundance in DLBCL appear to regulate the expression of genes involved in metabolism, cell cycle, and protein modification. Additionally, these miRNAs, including one candidate novel miRNA, miR-10393-3p, appear to target chromatin modification genes that are frequent targets of somatic mutation in non-Hodgkin lymphomas.<h4>Conclusions</h4>Our comprehensive sequence analysis of the DLBCL miRNome identifies candidate novel miRNAs and miRNAs associated with survival, reinforces results from previous mutational analyses, and reveals regulatory networks of significance for lymphomagenesis.Comprehensive miRNA sequence analysis reveals survival differences in diffuse large B-cell lymphoma patients.Lim Emilia L EL, Trinh Diane L DL, Scott David W DW, Chu Andy A, Krzywinski Martin M, Zhao Yongjun Y, Robertson A Gordon AG, Mungall Andrew J AJ, Schein Jacqueline J, Boyle Merrill M, Mottok Anja A, Ennishi Daisuke D, Johnson Nathalie A NA, Steidl Christian C, Connors Joseph M JM, Morin Ryan D RD, Gascoyne Randy D RD, Marra Marco A MADLBCL, diffuse large B-cell lymphoma.Histiocytic Lymphoma, DLBCL, Histiocytic, diffuse large B-cell lymphoma, patient, Diffuse, Diffuse Large-Cell, miRNA-HTS, Large-Cell, Diffuse Large B Cell Lymphoma, Diffuse Histiocytic Lymphomas, Large Cell Lymphoma, Diffuse Large Cell Lymphoma, microRNA-seq, Client., Large Lymphoid Lymphoma, Histiocytic Lymphomas, Patient, Large B-Cell, Clients, microRNA-seq assay, Lymphoma, Diffuse Histiocytic Lymphoma, Diffuse Large B-Cell Lymphoma, Diffuse Large-Cell Lymphomas, Large Cell, Diffuse Large Cell, miRNA-seq, Diffuse Large-Cell Lymphoma, Large Lymphoid, Diffuse Histiocytic, Large-Cell LymphomaRNA, Sequence Determination, stRNA, Small Temporal RNA, Primary, Determinations, Small, Diffuse Large B Cell Lymphoma, Micro RNA, survival, Client., Large Lymphoid Lymphoma, Sequence, Large B-Cell, Analysis, Large Cell, pre-miRNA, Diffuse Large Cell, Diffuse Large-Cell Lymphoma, Large-Cell Lymphoma, pri miRNA, Histiocytic Lymphoma, DLBCL, miRNAs, Small Temporal, death rate, Micro, Analyses, Determination, Histiocytic, diffuse large B-cell lymphoma, Temporal RNA, Primary MicroRNA, miRNA, Primary miRNA, Sequence Determinations, pri-miRNA, INSDC_feature:ncRNA, Diffuse, Diffuse Large-Cell, Large-Cell, Diffuse Histiocytic Lymphomas, Large Cell Lymphoma, Diffuse Large Cell Lymphoma, Histiocytic Lymphomas, Patient, time of survival, Clients, Lymphoma, Diffuse Histiocytic Lymphoma, MicroRNA, Diffuse Large B-Cell Lymphoma, Diffuse Large-Cell Lymphomas, pre miRNA, Large Lymphoid, Diffuse Histiocytic, Sequence AnalysesIPI, Ribonucleic, Formol, B Cells, Materials, Sequence Determination, B cell, Metabolic Concepts, bar, Germinoblastoma, Tumor, IDOL, DNA replication-independent chromatin organization, dmTAF[[II]]230, Small, Compared, Methanal, Accepted, Diffuse large B-cell lymphoma, First Line Treatment, Analysis, Metabolism Concept, Lymphomas, Non Polyadenylated, Cell Division Cycles, protein modification, TFIID TAF250, Involvement, Analyses, cel, Paraffin, catabolism, result, Tissue, Oxomethane, Comparison, metabolic process resulting in cell growth, miRNA, Sequence Determinations, miRNA-HTS, Somatic Mutation Abnormality, CF, high frequency, Familiar, Homo sapiens disease, Diffuse Large B-Cell Lymphoma, process resulting in protein modification, Idol, cellular protein modification process, MIR214 wt Allele, Comprehensive, Tumors, dTAF[[II]]230, Index, Polyadenylated, B Lymphocytes, 6.3.2.-, metabolism resulting in cell growth, TAF200, CENTRAL AFRICAN REPUBLIC, international_prognostic_index, Curative, CG4637, Candidate, microRNA-seq, Benign, secretion, Ribonucleic acids, simple tissue, pre-miRNA, pri miRNA, Polyadenylated Messenger RNA, Acid, statistical significance, miRNAs, Non Polyadenylated mRNA, protein_coding_transcript, death rate, MicroRNA 214 wt Allele, Mira, Benign Neoplasms, Inducible degrader of the LDL-receptor, Germinoblastomas, Non-Polyadenylated mRNA, Malignant Neoplasms, first-line therapy, DNA replication-independent chromatin assembly, GN, Taf250, B-Lymphocyte, Material, Lymphoma, MIRA, MicroRNA, Previous, Poly(A) RNA, TAF230, hg, HH, Fresh, Processes, stRNA, FRESH, Neoplasms, Specimen Appearance, chromatin assembly/disassembly, Metabolic Processes, Available, Somatic Mutation, Hh, Gene Products, disease or disorder, First Line Therapy, International Prognostic Index, Central African Republic, Cycles, DLBCL, Sarcomas, Negation, Guinea, dTAF[[II]]250, MONDOA, cell, centroblast, Cell Division Cycle, cell-division cycle, Target, messenger RNA, Metabolic Concept, Former, Cured, outcome, Neoplasias, dTAF250, template RNA, Formalin, Abundance, bar-3, Statistically Significant, Expression, bHLHe36, Leukemogenesis, pre miRNA, Including, Cancer, Sequence Analyses, New, RNA, Malignant Neoplasm, degradation, Myosin regulatory light chain interacting protein, CURATIVE, Diffuse Large B-Cell Lymphoma (DLBCL), Result, disorders, Messenger RNA, RNS, Primary, BG:DS00004.13, Cell, Availability, dTAF230, Concept, AW228700, Paraffin-Embedded Specimen, MT, Have, PARAFFIN-EMBEDDED, Poly(A)+ mRNA, Neoplasm, INSDC_feature:mRNA, TAF[[II]]250/230, condition, Germinoblastic Sarcomas, 324, Lymphomagenesis, background, metabolism, Cluster Analyses, Metabolic Phenomenon, Taf[[II]]250, Destination, multicellular organism metabolic process, primary cancer, mRNA, Regulator, Temporal RNA, increased number, Bursa-Equivalent Lymphocyte, Ribonucleic Acid, Cancers, Negated, malignant tumor, No, Oxomethylene, anon-WO0182946.19, target lesion, Polyadenylated mRNA, miRNA-seq, Neoplasia, Anabolism, Origin, biochemical pathways, mRNA Expression, Metabolic Process, Previously, cure, Bursa-Dependent Lymphocytes, Significant, Specimen Appearance Assessment, Fresh Specimen, First line of therapy, Malignant Lymphomas, anon-WO0134654.19, DmelCG4637, diseases, Statistical Significance, primary treatment, Concepts, diseases and disorders, Mir, MIR, Phenomenon, RNA Gene Products, gene expression, hsa-mir-214, Reticulolymphosarcoma, Miranda, increased, Targeting, human disease, Small Temporal, DNA replication-independent nuclesome assembly, diffuse large B-cell lymphoma, Determination, statistically significant, Polyadenylated Messenger, Formaldehyd, mir-214, mir, Primary miRNA, pri-miRNA, INSDC_feature:ncRNA, Novel, Malignant Lymphoma, Sarcoma, Cure, B lymphocyte, malignant neoplasm, Had, 140, Cell Cycles, biotransformation, Malignancies, Outcome, Catabolism, Micro RNA 214 Gene, Has, somatic mutation, 9430057C20Rik, TARGET, Process, ribose nucleic acid, ribonucleic acids, Small Temporal RNA, TAFII-250, TAF250/230, results, Significance, Division Cycles, Determinations, CG12249, Gene Expression, TAFII250, DNA replication-independent nucleosome organisation, Reticulolymphosarcomas, Involved, significant, Non, Ribonukleinsaeure, Abundant, bar3, Diseases, pentosenucleic acids, Genetic Materials, Not, Germinoblastic, fixed, Genetic Material, chromatin assembly, Clusterings, primary therapy, l(3)neo56, l(3)neo57, Micro, Division Cycle, CG17603, TAF[[II]], APPEAR, disease, Patient, Expressed, Cluster, SR3-5, Clustering, Cistron, accessory, other disease, chromatin modification, d230, Non-, Benign Neoplasm, Gene, dTAFII250, Established, Compare, EfW1, Malignant, Germinoblastic Sarcoma, supernumerary, Paraffin Embedded Tissue, dmTAF1, Messenger, Taf230, Metabolism, Cycle, First-Line Treatment, Metabolism Phenomena, TAF250, Taf200, B-cell, Genetic, Malignancy, Mrt, Taf1p, Cell Division, Positive Surgical Margin, non-neoplastic, Non-Polyadenylated RNA, Myosin regulatory light chain-interacting protein, Leukemogenesis/Lymphomagenesis., miRNA214, chromatin assembly or disassembly, time of survival, Clients, microRNA-seq assay, disorder, Known, TAF, Possess, FORMER, l(3)hh, MIRN214, Paraffin Block, TAF[[II]]250, target_lesion, Target Lesion Identification, Regulatory, Targeted, l(3)84Ab, medical condition, GUINEA, Cistrons, Client, Metabolic Phenomena, Metabolism Concepts, Micro RNA, survival, CAF, Sequence, yeast nucleic acid, p230, GIN, Phenomena, TFIID, FORMALIN, DmelCG12249, transcription-coupled nucleosome assembly, Polyadenylated RNA, international prognostic index, ribonucleic acid, Poly(A)+ RNA, TAF[[II]]230, frequent, distinct, biodegradation, Poly(A) Tail, Metabolic, Non Polyadenylated RNA, Non-Polyadenylated, Primary MicroRNA, TAF[II]250, Methylene oxide, introduction, present in greater numbers in organism, DmelCG17603, Inclusive, B-lymphocyte, First-Line Therapy, Positive Margins, TAF1falseMarra_DLBCL_discovery - samplesmiRNA-seq Cohort of 92 Fresh Frozen Diffuse Large B-cell Lymphoma Patient Samples2017-07-26 15:39:25EGAD00001001074960625723320EGAC00000000011EGAS00001001025