{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001001418"],"host":["EGA"],"description":["EGA study EGAS00001001418"],"dataset_title":["Landscape of AL mutations"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["amyloidosis AL, Plasma, WES, Complete Transcriptome, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Complete Exome Sequencings, primary systemic amyloidosis, Complete Exome, Plasmacytes, Complete Exome Sequencing, Whole Transcriptome Sequencing, Exome, amyloidosis primary systemic, primary systemic AL amyloidosis, primary AL amyloidosis, systemic AL amyloidsis., Sequencing, Cell, Plasmacyte, Exome Sequencing, Whole Exome, Light chain amyloidosis, Whole, Cells, Whole Exome Sequencing, Whole Transcriptome, Transcriptome Sequencing, Plasma Cell, Transcriptome Sequencings"],"description_synonyms":["Forms, Plasma Cell Dyscrasia, Ribonucleic, Materials, determination, Plasmacytes, Blood, activation of MAPK activity during sporulation, Progress Reports, Xkl-1, protein, RCC1, Rcc1, congenital defects, aplasia, Mutations, Immunoglobulins, School-Age, KL receptor activity, systemic amyloidosis, %, Gsfsco1, diseases, Abc8, rcc1, Summary Report, symptoms, SCO5, diseases and disorders, Aggregates, Whole Transcriptome, Transcriptome Sequencing, SCO1, Mutations., protein aggregate, Gsfsow3, MTCP1, Gsfsco5, EBVS, Summary Reports, Non Polyadenylated, RNA Gene Products, SOW3, NCMS, Progression, systemic, sdt, amyloidosis, N-ras, human disease, thymus nucleic acid, Occidental, xrcc1, Progress Report, Complete Exome Sequencing, Whole Transcriptome Sequencing, 4931417M11Rik, hypoplasia, myeloma, W, Substance, Amyloid, FELL, genetic, Progress, LYP, Field Reports, no ICD-O subtype (morphologic abnormality), Exacerbation, Bs, Homo sapiens disease, Paraimmunoglobulinemias, Double-Stranded DNA, deoxyribonucleic acids, DNAn, TL, Plasma Cell, Sl, Aggregate, screening, Serum amyloid P-component(1-203), Gammopathy, ribose nucleic acid, AW413978, Myeloma, effector B-cell, DmelCG10480, Exome, ribonucleic acids, Disease Exacerbation, familial, Tr-kit, white, Double-Stranded, beta-D-fructofuranosyl, not genetically inherited, deformities, MGUS - Monoclonal gammopathy of uncertain significance, (Deoxyribonucleotide)n+m, Amyloid Fibrils, PBT, Investigative Report, FEEL-2, European, School Age, Ribonukleinsaeure, Diseases, chc1-a, kl1-A, Corpuscles, pentosenucleic acids, Genetic Materials, Light Chains, Protein Aggregate, NOS, Ribonucleic acids, median, FEEL2, KIT, IMD5, desoxyribose nucleic acid, morphology (morphologic abnormality), Genetic Material, activation, Caucasians, chc1-b, tyrosine-protein kinase Kit, atresia, Acid, pbt, Blood Cell, Populations, Complete Transcriptome, STERILE APETALA, Amyloid Substance, amyloidoses, MFEEL-2, 9.5S alpha-1-glycoprotein, HARE, alpha-D-Glucopyranoside, Field, effector B cell, inxs, malformations, NRAS, Exomes, signs, INSDC_feature:gene, kit, Gammapathy, Plasmacyte, Ig Light Chains, disease, Corpuscle, Report, multiple, BJ1, Patient, Material, PBMCs, anomalies, Cells, ds DNA, Whole Exome Sequencing, White, Cistron, Gm686, inherited genetic, Blood Corpuscles, School-Age Population, Multiple myeloma (clinical), DNA, Transcriptome Sequencings, AV095280, Bone, krk1, Immunoglobulin Light Chain, other disease, whole exome, dRCC1, STAB-2, DNS, Monoclonal gammopathy of uncertain significance, Immunoglobulin, Monoclonal Gammapathies, (Deoxyribonucleotide)n, Complete Exome, Multiple myeloma (disorder), Kahler's disease, Light-Chain, NS6, number, SCF receptor activity, Gene, Amyloid Fibril, primary AL amyloidosis, protein-containing complex, Monoclonal Gammopathy Of Undetermined Significance (MGUS), presence, Deoxyribonucleic acids, Bone Marrow Cell, Buffer, Light Chain, HEL-S-92n, Investigative, Caucasian, Deoxyribonucleic Acid, scfr, Immunoglobulin Light-Chain, PBMC, [M]Plasma cell myeloma, Gene Products, DNA Damage Response, Clinical Progression, disease or disorder, ALPS4, amyloid, SNHG3-RCC1, Monoclonal Gammopathies, defects, Paraproteinemia, SCFR, Blood Corpuscle, Immunoglobulin Light, Paraimmunoglobulinemia, Ig, Plasmacytic myeloma, study, School-Age Populations, WES, Fdc, Ig Light, Complete, Exome Sequencings, Multiple myeloma, Genetic, Clinical, class switch recombination, Monoclonal gammopathy of undetermined significance, amyloidosis (disease), homopolymer, Chc1, amyloidosis primary systemic, Double Stranded, monoclonal gammopathy, Deoxyribonucleic acid, primary systemic AL amyloidosis, Chromosome 11, Population, Sequencing, Bone Marrow, Genotypes, isotype switch recombination, non-neoplastic, Non-Polyadenylated RNA, Marrow Cell, Light Chain Immunoglobulins, Whole Exome, Clinical Course, Clients, CHC1, Whole, disorder, (Deoxyribonucleotide)m, School Age Population, Investigative Reports, Monoclonal gammopathy of undetermined significance (morphologic abnormality), constitutitional genetic, myeloma - multiple, chc1, proto-oncogene c-Kit, RNA, Disease, findings, RCC1-I, Complete Exome Sequencings, whole blood, Marrow Cells, NRAS1, protein complex, DNAn+1, AI326872, Proteins, disorders, SAP|SH2D1A, RNS, medical condition, Monoclonal, Monoclonal Gammopathy, buffer, Cistrons, Plasma Cell Dyscrasias, MGUS, Client, Cell, systemic AL amyloidsis, Al amyloidosis, multiple myeloma, CG18640 (Bj1), Exome Sequencing, count in organism, plasma B cell, native protein, Genogroup, Light-Chain Immunoglobulins, KIT ligand receptor activity, yeast nucleic acid, agenesis, Protein, Research Reports, chemical analysis, CMNS, class switching, condition, XLPD1, Myelomatosis, ds-DNA, Monoclonal Gammapathy, MULT MYELM W/O REMISSION, amyloid disease, Cell Dyscrasia, Caucasoid, plasmocyte, Monoclonal Gammopathy of Unknown Significance, XKrk1, RanGEF, Fibril, Monoclonal gammopathy of uncertain significance (disorder), amyloidosis AL, Plasma, XLPD, ribonucleic acid, SAP, plasma B-cell, c-KIT, Complete Transcriptome Sequencing, Cytogenetic, Peripheral Blood, primary systemic amyloidosis, Chains, Non Polyadenylated RNA, Non-Polyadenylated, plasma cell disorder, patient, Ribonucleic Acid, CD117, School Age Populations, XLP, Xlp, Multiple myeloma without mention of remission, Reticuloendothelial System, Protein Gene Products, Gene Proteins, Genogroups, Benign Monoclonal Gammopathy, c-kit, Fibrils, Light chain amyloidosis, no ICD-O subtype, Reports, Plasma Cell Myeloma, C-Kit, Whites, Ssm, plasmacyte, birth defects, cardinality, MXH1.20, Desoxyribonukleinsaeure, xkl-1, MXH1_20, Paraproteinaemia, assay, DSHP, Summary, FEX2, hereditary, Dyscrasia, CG10480, PTX2, Field Report"],"additional_accession":[]},"is_claimable":false,"name":"Exome Sequencing to Define the Landscape of Plasma Cells in Systemic Light chain Amyloidosis","description":"Systemic light chain amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils in different organs, where they form toxic protein aggregates. The underlying disease is a plasma cell disorder, but limited whole exome data are available. We report the findings of an exome sequencing study in AL to define a plasma cell signature and compare this to monoclonal gammopathy of undefined significance (MGUS) and myeloma (MM). \nTwenty-four samples from unselected newly diagnosed untreated AL patients were analysed. CD138+ cells were isolated from bone marrow cells using MACSorting (Miltenyi Biotech, Bisley, UK). Cells were lysed in RLT+ buffer and DNA/RNA extracted using the AllPrep kit (Qiagen, Manchester, UK). Peripheral blood was isolated from patients, white blood cells purified by Ficoll-Pacque and DNA extracted using the QIAamp DNA mini kit (Qiagen). \nThere were a median of 47 acquired nonsynonymous variants (range 4-253) per patient. Thirty percent of patients yielded a mutation in a myeloma driver gene. These mutations were either clonal or sub-clonal. There was evidence of MAPK activation with NRAS mutations, NF-κB activation and DNA repair pathway alterations. Exome data were used to determine the cytogenetic groups of AL samples and identified hyperdiploidy in 33% of cases and t(11;14) in 33% of cases. All translocations were generated via class switch recombination and breakpoints on chromosome 11 fell into the expected regions. A novel translocation, unlikely to be driving disease progression was identified involving RCC1. Finally, further analysis of the APCS gene encoding for the SAP protein did not show any biased genotype in the AL population in comparison to the general population. We conclude that exome sequencing identifies a genetic make-up of AL that is similar to other plasma cell disorders such as MM and MGUS. This not only includes copy number abnormalities and translocations but also nonsynonymous mutations.","dates":{"updated":"2018-09-20 09:50:58"},"accession":"EGAS00001001418","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001001861","EGAC00001000377"]}}