title: Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
abstract: To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138(+) plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters described in the University of Arkansas for Medical Science (UAMS) classification, CD-1 (n = 13, 4.1%), CD-2 (n = 34, 1.6%), MF (n = 32, 1.0%), MS (n = 33, 1.3%), proliferation-associated genes (n = 15, 4.7%), and hyperdiploid (n = 77, 24.1%). Moreover, the UAMS low percentage of bone disease cluster was identified as a subcluster of the MF cluster (n = 15, 4.7%). One subgroup (n = 39, 12.2%) showed a myeloid signature. Three novel subgroups were defined, including a subgroup of 37 patients (11.6%) characterized by high expression of genes involved in the nuclear factor kappa light-chain-enhancer of activated B cells pathway, which include TNFAIP3 and CD40. Another subgroup of 22 patients (6.9%) was characterized by distinct overexpression of cancer testis antigens without overexpression of proliferation genes. The third novel cluster of 9 patients (2.8%) showed up-regulation of protein tyrosine phosphatases PRL-3 and PTPRZ1 as well as SOCS3. To conclude, in addition to 7 clusters described in the UAMS classification, we identified 3 novel subsets of multiple myeloma that may represent unique diagnostic entities.
authors.affiliation: Department of Hematology, Erasmus Medical Center and University, Rotterdam, The Netherlands. a.broyl@erasmusmc.nl
authors.forename: Annemiek
authors.initials: A
authors.lastname: Broyl
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Henk
authors.initials: H
authors.lastname: Lokhorst
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Knegt
authors.forename: Justine
authors.initials: J
authors.lastname: Peeters
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Uta
authors.initials: U
authors.lastname: Bertsch
authors.forename: Arjan
authors.initials: A
authors.lastname: Buijs
authors.forename: Marian
authors.initials: M
authors.lastname: Stevens-Kroef
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Kersten
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Laila
authors.initials: L
authors.lastname: el Jarari
authors.forename: George
authors.initials: G
authors.lastname: Mulligan
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Mark
authors.initials: M
authors.lastname: van Duin
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D016000:Cluster Analysis; D005060:Europe; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D010950:Plasma Cells / Q000378:metabolism*; D053668:Syndecan-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D053668:Syndecan-1