EGAGenomicsIllumina HiSeq 4000;ILLUMINAhttps://ega-archive.org/datasets/EGAD000010041131281EGA dataset EGAD00001004113EGAThe purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.Chavan S S SS, He J J, Tytarenko R R, Deshpande S S, Patel P P, Bailey M M, Stein C K CK, Stephens O O, Weinhold N N, Petty N N, Steward D D, Rasche L L, Bauer M M, Ashby C C, Peterson E E, Ali S S, Ross J J, Miller V A VA, Stephens P P, Thanendrarajan S S, Schinke C C, Zangari M M, van Rhee F F, Barlogie B B, Mughal T I TI, Davies F E FE, Morgan G J GJ, Walker B A BAPlasma-Cell Myelomas, RB1, Plasma-cell myeloma, Relapse, Disease, retinoblastoma-related 1, Myelomas, FBF, Myeloma, Multiple myeloma (disorder), Kahler's disease, rbf1, Cell Myelomas, RBF1., retinoblastoma, Myeloma Multiple, RBF, Myeloma-Multiples, Myeloma-Multiple, autosomal dominant, RETINOBLASTOMA 1, dRBF, hereditary retinoblastoma, Multiple Myeloma, MM, Al amyloidosis, multiple myeloma, RBR, Kahler, Multiple Myelomas, relapse, eye cancer, Recrudescence, [M]Plasma cell myeloma, Myelomatoses, OSRC, RB, rb, PPP1R130, ATRBR1, NOS, Myelomatosis, RETINOBLASTOMA PROTEIN, Relapses, rbf, MULT MYELM W/O REMISSION, morphology (morphologic abnormality), Plasma-Cell, Plasma-Cell Myeloma, Plasmacytic myeloma, systemic, Plasma, pRb, amyloidosis, Multiple myeloma, DmelCG7413, Recrudescences, pp110, Recurrences, Plasma Cell Myelomas, Rb, Rb-1, myeloma, Kahler Disease, Multiple myeloma without mention of remission, Rb1, Multiple, p105-Rb, no ICD-O subtype, Cell Myeloma, multiple, Plasma Cell Myeloma, familial retinoblastoma, no ICD-O subtype (morphologic abnormality), RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, CG7413, Multiple myeloma (clinical), RbF, EG:34F3.3, Plasma Cell, trilateral, somatic mutation, myeloma - multiple, Rbf1Vasp, VASP, DmelCG15112, ENHANCER OF ATNSI ACTIVITY, Data Set, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, 2018., ENA/VASPRB1, Materials, tumor suppressor, Plasmacytes, CRAF1, Cell Myelomas, (SP-4-2)-, RBF, AIP1, Tumor, congenital defects, mcIAP1, Myeloma-Multiples, Myeloma-Multiple, aplasia, Tp53, 13, RBR, relapse, cell cycle regulator, bbl, RB, rb, RETINOBLASTOMA PROTEIN, LAP1, Relapses, Analysis, rbf, 8, CD40bp Protein, T-BAM, treatment, systemic, amyloidosis, HAIP1, Prognoses, C77269, Gene Expressions, cIAP2, cIAP1, cIAP-2, cIAP-1, BCC7, Chromosome Marker, pp110, Multivariate Analyses, Recurrences, Rb, hypoplasia, myeloma, N24)-, hemes, AW047063, Cell Myeloma, Markers, no ICD-O subtype (morphologic abnormality), Ferrate(2-), CG4394, CCA4, disease management, CIAP2, Therapies, Malignancies, CG7413, Plasma Cell, somatic mutation, Tumors, Plasma-Cell Myelomas, Therapy, Relapse, retinoblastoma-related 1, Myelomas, AW107670, Myeloma, effector B-cell, rbf1, retinoblastoma, p18, MIAP2, MIAP1, RETINOBLASTOMA 1, deformities, hereditary retinoblastoma, Multiple Myeloma, CAP1, Kahler, AW146227, Protoheme, Benign, Recrudescence, Marker, Genetic Materials, ATRBR1, NOS, bfy, morphology (morphologic abnormality), Genetic Material, DmelCG4394, Plasma-Cell Myeloma, atresia, pRb, haeme, Factors, DmelCG7413, Genetic Marker, Prognostic, effector B cell, malformations, 17-tetramethyl-21H, p53., Benign Neoplasms, DNA Markers, AI528849, IAP2, IAP1, Treatments, INK4c, Plasmacyte, Malignant Neoplasms, INK4d, Multiple, p105-Rb, dTRAF3, multiple, Heme b, familial retinoblastoma, Chromosome, Material, Proliferation, anomalies, Cells, P53, p44, bhy, Cistron, p18INK4c, Multiple myeloma (clinical), DNA, Chromosome Markers, EG:34F3.3, INK4C, Rbf1, RBF1, Prognostic Factor, Proliferating, FBF, Multiple myeloma (disorder), Kahler's disease, Neoplasms, N23, (7, N22, p53, Benign Neoplasm, hem, Gene, Prognostic Factors, CAP-1, Malignant, LFS1, autosomal dominant, dRBF, hemos, Multiple Myelomas, eye cancer, RNF48, RNF49, [M]Plasma cell myeloma, Myelomatoses, OSRC, MAF, defects, Plasmacytic myeloma, c-MAF, study, CRAF1 Protein, p18-INK4C, Multiple myeloma, Genetic, Malignancy, Recrudescences, 18-dipropanoato(4-)-N21, proliferating, Plasma Cell Myelomas, haem, IIAE5, HIAP1, HIAP2, Expressions, Neoplasias, c-maf, Maf2, heme, Trp53, API2, Api2, Api1, Traf-related, 2810401A20Rik, Expression, TRP53, myeloma - multiple, Cancer, 12-diethenyl-3, CD40bp, Plasma-cell myeloma, Disease, Traf3, Malignant Neoplasm, Birc3, Birc2, 23H-porphine-2, Myeloma Multiple, Factor, Cistrons, Cell, Multivariate, Xp53, MM, Al amyloidosis, multiple myeloma, Haem, plasma B cell, c-IAP2, agenesis, Neoplasm, PPP1R130, MIHB, MIHC, Myelomatosis, TRAF3, MULT MYELM W/O REMISSION, LAP 1 Protein, Plasma-Cell, plasmocyte, Plasma, cMaf, amn, plasma B-cell, dihydrogen, MALT2, LAP-1 Protein, Rb-1, Kahler Disease, TNF Receptor Associated Factor 3, CD40 Receptor Associated Factor 1, Cancers, A230108G15Rik, Multiple myeloma without mention of remission, Rb1, DNA Marker, no ICD-O subtype, Therapeutic, Plasma Cell Myeloma, CD40 Receptor-Associated Factor 1, plasmacyte, birth defects, RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, TRAF-3, Treatment, RbF, trilateral, Protoheme IX, Neoplasia, FerroprotoporphyrinRibonucleic, BamF, biml, BamC, Plasmacytes, selection process, bam, Cell Myelomas, (SP-4-2)-, Foundation, Myeloma-Multiples, Myeloma-Multiple, Medical Specialties, 13, Speciality, smoldering Multiple myeloma/plasma cell myeloma, smouldering multiple myeloma, Specialities, medulla ossea, Mutations., DmelCG10422, 8, Non Polyadenylated, RNA Gene Products, systemic, amyloidosis, thymus nucleic acid, Insurance Medicine, Asymptomatic, HCAP, myeloma, N24)-, hemes, smouldering Multiple myeloma/plasma cell myeloma, CDLS3, Red Marrow, asymptomatic myeloma, Cell Myeloma, no ICD-O subtype (morphologic abnormality), medicine, Ferrate(2-), Red, Medicine, Double-Stranded DNA, Medicines, deoxyribonucleic acids, DNAn, Nucleotide, Plasma Cell, Plasma-Cell Myelomas, Specialties, Myelomas, smouldering myeloma, ribose nucleic acid, smoldering multiple myeloma, Myeloma, ribonucleic acids, ham, Double-Stranded, Multiple Myeloma, (Deoxyribonucleotide)n+m, MGUS - Monoclonal gammopathy of uncertain significance, Medical Speciality, Kahler, Protoheme, Ribonukleinsaeure, Specialty, pentosenucleic acids, NOS, Ribonucleic acids, desoxyribose nucleic acid, Smoldering Myelomas, morphology (morphologic abnormality), Plasma-Cell Myeloma, nucleotides, Acid, haeme, medulla of bone, 17-tetramethyl-21H, alpha, Plasmacyte, Insurance Medicines, Multiple, BIM, multiple, Heme b, Patient, ds DNA, Cells, SMC3L1, DNA, Multiple myeloma (clinical), Bone, Smoldering Myeloma, bim, DNS, Monoclonal gammopathy of uncertain significance, (Deoxyribonucleotide)n, Multiple myeloma (disorder), Kahler's disease, N23, (7, N22, hem, Monoclonal Gammopathy Of Undetermined Significance (MGUS), Smoldering Multiple Myelomas, hemos, Deoxyribonucleic acids, fs(3)neo61, CG10422, Multiple Myelomas, Medical Specialities, Deoxyribonucleic Acid, Marrow, [M]Plasma cell myeloma, Gene Products, Myelomatoses, bim-beta7, Yellow, Paraproteinemia, Medical, Plasmacytic myeloma, Multiple myeloma, bim-beta6, 18-dipropanoato(4-)-N21, Monoclonal gammopathy of undetermined significance, Plasma Cell Myelomas, haem, Double Stranded, Deoxyribonucleic acid, monoclonal gammopathy, smoldering plasma cell myeloma, BMH, Non-Polyadenylated RNA, drugs, heme, Clients, (Deoxyribonucleotide)m, Insurance, Monoclonal gammopathy of undetermined significance (morphologic abnormality), CSPG6, myeloma - multiple, 12-diethenyl-3, Plasma-cell myeloma, RNA, Disease, Medical Specialty, DNAn+1, RNS, 23H-porphine-2, BOD, Myeloma Multiple, Client, MGUS, Cell, MM, Al amyloidosis, multiple myeloma, Haem, Asymptomatic Multiple Myeloma, medulla ossium, yeast nucleic acid, Myelomatosis, bod, ds-DNA, MULT MYELM W/O REMISSION, bimel, Monoclonal Gammopathy of Unknown Significance, Plasma-Cell, Monoclonal gammopathy of uncertain significance (disorder), Plasma, ribonucleic acid, Yellow Marrow, asymptomatic plasma cell myeloma, dihydrogen, Asymptomatic Multiple Myelomas, medullary bone, Non Polyadenylated RNA, Non-Polyadenylated, Kahler Disease, Ribonucleic Acid, Smoldering, Multiple myeloma without mention of remission, Benign Monoclonal Gammopathy, no ICD-O subtype, Plasma Cell Myeloma, Bam-C, BAM, Bam, Desoxyribonukleinsaeure, smoldering myeloma, Paraproteinaemia, Protoheme IX, Ferroprotoporphyrinfalseena-DATASET-UAMS-09-05-2018-19:35:00:131-1808 - samplesDNA (n=1281) and RNA (n=767) were extracted from bone marrow aspirates where CD138+ selection had been performed to enrich plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). DNA and/or RNA were sent to Foundation Medicine where targeted sequencing was performed using their Foundation 1 Heme panel. Resulting BAM files were returned along with annotations for somatic events including single nucleotide mutations, indels and structural rearrangements.2018-05-17 14:50:59EGAD00001004113960628234347EGAC00001000845EGAS00001002874