EGAGenomicsCancer Genomicshttps://ega-archive.org/studies/EGAS00001006191EGAEGA study EGAS00001006191Molecular and clinical diversity in primary central nervous system lymphoma: a LOC network multi-omic PCNSL studyEGArestrictedstudy., primary lymphoma, CNSF24B9.2, Ribonucleic, Formol, SEC1, T22F8.160, Activity, determination, CS-1, and rna binding 2, Feature, MEE6, Chronic Airflow Obstructions, Cs-1, chronic obstructive pulmonary disease (COPD), DNA Methylations, Germinoblastoma, Tumor, Medical Specialties, Mutations, Classifications, Malignant Lymphomas, Speciality, hierarchies, hierarchy, diseases, T22F8_160, alcagamma, Specialities, HOT, systematics, responsivity, Methanal, Parafilm, ATGPR7, chronic obstructive airways disease NOS (disorder), Chronic irreversible airway obstruction, GRP8, diseases and disorders, GRP7, Whole Transcriptome, Transcriptome Sequencing, Chronic Obstructive Pulmonary Disease (COPD), Lymphomas, Non Polyadenylated, RNA Gene Products, Reticulolymphosarcoma, imprinted and ancient gene protein, treatment, CRACC, human disease, ADHFe1, COLD (chronic obstructive lung disease), Insurance Medicine, DNA methylation maintenance, Prognoses, Genomes, 1.1.99.24, NEC in ICD9CM_2006, dJ221C16.5, ADH8, Complete Exome Sequencing, H1.4, Whole Transcriptome Sequencing, mKIAA4134, Tissue, Formaldehyd, Oxomethane, ATAPX1, CAFL - Chronic airflow limitation, CD319, DNA methylation, Chronic airflow limitation, Malignant Lymphoma, set, Sarcoma, disease (COPD), GLYCINE RICH PROTEIN 7, H14, medicine, disease management, Therapies, F24B9_2, Medicine, H1-4, Homo sapiens disease, stage, Malignancies, Consensus Development, Medicines, ascorbate peroxidase 1, glycine-rich RNA-binding protein 8, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, H1E, Tumors, Therapy, CHRONIC, Specialties, chronic obstructive lung disease [Ambiguous], obstructive lung disease, wide/broad, ribose nucleic acid, SPAG13, Exome, ribonucleic acids, Systematics, H1d, results, Airflow Obstructions, H1e, mKIAA0726, CHRONIC OBSTRUCTIVE AIRWAY DIS, pulmonary disease (COPD), Taxonomies, Medical Speciality, Reticulolymphosarcomas, Benign, l(3)SH16, rop(Sec1), Ribonukleinsaeure, CHRONIC OBSTRUCTIVE, Diseases, chronic obstructive pulmonary disease and allied conditions, Specialty, Chronic airway disease, pentosenucleic acids, NOS, simple tissue, Ribonucleic acids, Germinoblastic, CDHR13, Airflow Obstruction, fixed, ras2, COPD NOS, CHRONIC OBSTRUCTIVE LUNG DIS, GLYCINE-RICH PROTEIN 8, Chronic Obstructive Airways Disease, Acid, Chronic airway obstruction, Chronic obstructive lung disease, Complete Transcriptome, Factors, Immunotherapies, polycomb repressive complex 2, cold, ASCORBATE PEROXIDASE, Prognostic, Benign Neoplasms, MLYM, whole genome, Germinoblastomas, Features, Treatments, Alcohol dehydrogenase iron-containing protein 1, Malignant Neoplasms, Chronic Airflow Obstruction, Insurance Medicines, disease, wide, lymphoma, F2G1.4, Patient, OBSTRUCTIVE PULMONARY DISEASE (COPD), COPD - Chronic obstructive pulmonary disease, Lymphoma, Whole Exome Sequencing, chronic obstructive airways disease, ATAPX01, DNA, obstructive pulmonary disease (COPD), DmelCG15811, E430016J11Rik, other neoplasm, Transcriptome Sequencings, COLD, chronic obstructive lung disease, Methylation, Gruppe, Prognostic Factor, other disease, Cas1, Extra Sex Combs/Enhancer of Zeste complex, Complete Exome, taxonomy, DISEASE (COPD), Neoplasms, developmental stage, Benign Neoplasm, number, CAO - Chronic airflow obstruction, Prognostic Factors, H1f4, CHRONIC OBSTRUCTIVE PULM DIS, circadian rhythm, broad, Development, 19A, Chronic obstructive pulmonary disease NOS, Malignant, Germinoblastic Sarcoma, Ximpact, presence, and RNA binding 1, Chronic obstructive pulmonary disease finding, Cold, PULMONARY DISEASE (COPD), Medical Specialities, Pulmonary Disease, Consensus, susceptible, Gene Products, disease or disorder, Medical, Sarcomas, reactivity, WES, Cold Temperatures, Taxonomy, Complete, Exome Sequencings, CNS, PRC2 complex, Malignancy, l(3)64Ah, Hist1h1c, Hist1h1e, Chronic Obstructive, Sequencing, CSTN3, CSTN2, non-neoplastic, Non-Polyadenylated RNA, Neoplasias, Whole Exome, drugs, Formalin, Catl, ATGRP7, grupos, ATGRP8, Clients, Cst-3, Whole, NEC, heterogeneity, Cst-2, disorder, Chronic, Characteristics, H1F4, Insurance, Methylations, Cancer, COPD, RNA, COAD - Chronic obstructive airways disease, Malignant Neoplasm, Complete Exome Sequencings, grupo, chronic obstructive airways disease NOS, Medical Specialty, not elsewhere classified, COAD, disorders, H1var2, RNS, medical condition, Factor, COLD - Chronic obstructive lung disease, maternal effect embryo arrest 6, Client, impact-a, chronic, PULM DIS CHRONIC OBSTRUCTIVE, group, Chronic obstructive pulmonary disease finding (finding), Fe-containing alcohol dehydrogenase, Cs3, Cs2, Exome Sequencing, count in organism, Characteristic, Temperatures, yeast nucleic acid, chemical analysis, Neoplasm, condition, imprinted and ancient gene protein homolog, IMPACT, ROP, Germinoblastic Sarcomas, FORMALIN, GLYCINE-RICH RNA-BINDING PROTEIN 7, (COPD), chronic airway obstruction, chronic obstructive, CAL - Chronic airflow limitation, ALC-GAMMA, cs1, CS1, chronic obstructive airway disease, ribonucleic acid, Temperature, AI448973, CS2, Complete Transcriptome Sequencing, distinct, ensemble, Non Polyadenylated RNA, Dops, GR-RBP7, Non-Polyadenylated, rop, Rest, GR-RBP8, Cancers, Ribonucleic Acid, Methylene oxide, H1s-4, CG15811, 2900042C18Rik, Therapeutic, Oxomethylene, Cat01, cardinality, chronic obstructive lung disease (disorder), Treatment, cold (chronic obstructive lung disease), PRC2, assay, KRAP, Chronic Obstructive Lung Disease, primary lymphoma, response, variable, CNS., groupe, General activity, RWDD5, Neoplasia, lymphoid cancer, chronic obstructive pulmonary diseasefalseMolecular and clinical diversity in primary central nervous system lymphoma: a LOC Network studyPrimary central nervous system lymphoma (PCNSL) is a distinct extranodal lymphoma presenting with limited stage disease but variable response rates to treatment despite homogenous pathological presentation. The likely underlying molecular heterogeneity and its clinical impact is poorly understood. We performed a comprehensive genome-wide analysis of 147 PCNSL from fresh-frozen tumor tissue from immunocompetent, treatment naïve PCNSL patients, employing whole-exome sequencing, assessment of somatic copy number alterations and DNA methylation, and RNA expression. These data were integrated and correlated with the clinico-radiological characteristics and outcomes of the patients. We validated our results in an independent series of 93 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples. Consensus clustering of multi-omics data identified four robust, non-overlapping, prognostically significant clusters (CS) within PCNSL. The CS1 group, characterized by high proliferation and Polycomb Repressive Complex 2 (PRC2) complex activity had an intermediate outcome between CS2/CS3 and CS4. Patients who had PCNSL with an “immune-hot†(CS4) profile had the most favorable clinical outcome. In contrast, patients with the immune-cold hypermethylated CS2 and the heterogenous-immune CS3 groups had a poor prognosis. Nearly all PCNSL patients with meningeal infiltration harbored HIST1H1E mutations, enriched in the CS3 group. The integrated analysis suggests that the CS4 group may be more susceptible to immunotherapy. The integration of genome-wide data from multi-omics data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that significantly improved the current clinical stratification. This molecular classification using FFPE samples facilitates routine use in clinical practice and provides potential precision-medicine strategies in PCNSL.2022-11-23 11:37:25EGAS000010061919606EGAD00001008706EGAC00001002640