title: The glycome of normal and malignant plasma cells.
abstract: The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma.
authors.affiliation: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany ; Translationale Immunologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Moehler
authors.affiliation: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany ; Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.affiliation: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany ; Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: Pathologisches Institut, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Andrulis
authors.affiliation: INSERM, U1040, Montpellier, France ; Centre Hospitalier Universitaire, Montpellier, Institute of Research in Biotherapy, 3 Montpellier, France ; Université Montpellier 1, UFR Médecine, Montpellier, France.
authors.forename: Jèrôme
authors.initials: J
authors.lastname: Moreaux
authors.affiliation: Abteilung für Biostatistik, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.affiliation: Translationale Immunologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Willhauck-Fleckenstein
authors.affiliation: Translationale Immunologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Merling
authors.affiliation: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Bertsch
authors.affiliation: Institut für Humangenetik, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.affiliation: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany ; Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: INSERM, U1040, Montpellier, France ; Centre Hospitalier Universitaire, Montpellier, Institute of Research in Biotherapy, 3 Montpellier, France ; Université Montpellier 1, UFR Médecine, Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
authors.affiliation: Translationale Immunologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwartz-Albiez
mesh_terms: D016000:Cluster Analysis; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054794:Glycomics; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D010950:Plasma Cells / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D017261:Glycosylphosphatidylinositols; D006497:Heparan Sulfate; D008364:Mannosyltransferases; D011134:Polysaccharides; C486036:PIGM protein, human