title: The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
abstract: The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an early and deep tumour burden reduction, up to the level of complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC obtained at baseline from MM patients in CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from MM with subsequent optimal response to primary induction therapy.By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%-85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation might explain patients' sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients.
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Terragna
authors.affiliation: Department of Physics and Astronomy (DIFA), Bologna University, Bologna, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Martello
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pantani
authors.affiliation: Clinica Ematologica, DISM, University of Udine, Udine, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pezzi
authors.affiliation: Department of Physics and Astronomy (DIFA), Bologna University, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Levi
authors.affiliation: Clinica di Ematologia, A.O.U. Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.affiliation: U.O Oncologia Medica, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Proserpio
authors.affiliation: Ematologia Clinica, A.O.U. Ospedali Riuniti, Trieste, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Sabbata
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.affiliation: Hematology Division UTMO, Azienda "Ospedali Riuniti Villa Sofia-Cervello" Presidio Ospedaliero V.Cervello, Palermo, Italy.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Cangialosi
authors.affiliation: S.C.Oncologia Medica, A.O. Sant'Antonio Abate, Gallarate, Varese, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ciambelli
authors.affiliation: Unità Operativa di Ematologia, Istituti Ospitalieri di Cremona, Cremona, Italy.
authors.forename: Clara Virginia
authors.initials: CV
authors.lastname: Viganò
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Flores Angela
authors.initials: FA
authors.lastname: Dico
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Santacroce
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Borsi
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Brioli
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Marzocchi
authors.affiliation: Department of Physics and Astronomy (DIFA), Bologna University, Bologna, Italy.
authors.forename: Gastone
authors.initials: G
authors.lastname: Castellani
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: "Seràgnoli" Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012074:Remission Induction; D013792:Thalidomide / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone
keywords: SNPs; VTD; complete response; gene expression profile; multiple myeloma