title: Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?
abstract: The prognosis of multiple myeloma is mainly dependent upon chromosomal changes. The 2 major abnormalities driving poor outcome are del(17p) and t(4;14). However, the outcome of these high-risk patients is not absolutely uniform, with some patients presenting long survival. We hypothesized that these better outcomes might be related to concomitant "good-risk" chromosomal changes exploring hyperdiploidy. We analyzed a large series of 965 myeloma patients, including 168 patients with t(4;14) and 126 patients with del(17p), using high-throughput single-nucleotide polymorphism arrays after plasma cell sorting. As expected, trisomic chromosomes were highly associated. Using the LASSO model, we found that only chromosome 3, when trisomic, was associated with a longer progression-free survival and that 3 trisomies modulated overall survival (OS) in myeloma patients: trisomies 3 and 5 significantly improved OS, whereas trisomy 21 worsened OS. In patients with t(4;14), trisomies 3 and/or 5 seemed to overcome the poor prognosis. For the first time, using a specific modeling approach, we show that not all trisomies display the same prognostic impact. This finding could be important for routine assessment of prognosis in myeloma, and some high-risk patients with a traditional evaluation could in fact be standard-risk patients.
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Dijon, France;
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Chretien
authors.affiliation: Unit for Genomics in Myeloma, Institut Universitaire du Cancer-Oncopole, and Centre de Recherches sur le Cancer de Toulouse INSERM 1037, Toulouse, France;
authors.forename: Jill
authors.initials: J
authors.lastname: Corre
authors.affiliation: Service d'Epidemiologie, Centre Hospitalier Universitaire, Toulouse, France;
authors.forename: Valerie
authors.initials: V
authors.lastname: Lauwers-Cances
authors.affiliation: Unité Mixte de Génomique du Cancer, Centre Hospitalier Universitaire, and INSERM U892, Nantes, France;
authors.forename: Florence
authors.initials: F
authors.lastname: Magrangeas
authors.affiliation: Unit for Genomics in Myeloma, Institut Universitaire du Cancer-Oncopole, and Centre de Recherches sur le Cancer de Toulouse INSERM 1037, Toulouse, France;
authors.forename: Alice
authors.initials: A
authors.lastname: Cleynen
authors.affiliation: Service d'Epidemiologie, Centre Hospitalier Universitaire, Toulouse, France;
authors.forename: Edwige
authors.initials: E
authors.lastname: Yon
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Nancy, France;
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Lille, France;
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Department of Hematology, Centre Hospitalier, Annecy, France;
authors.forename: Frederique
authors.initials: F
authors.lastname: Orsini-Piocelle
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Nancy, France;
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Blade
authors.affiliation: Department of Hematology, Hopital Inter-Armées, Toulon, France;
authors.forename: Claudine
authors.initials: C
authors.lastname: Sohn
authors.affiliation: Department of Hematology, Centre Hospitalier, Toulon, France;
authors.forename: Lionel
authors.initials: L
authors.lastname: Karlin
authors.affiliation: Department of Hematology, Centre Hospitalier, Pau, France;
authors.forename: Xavier
authors.initials: X
authors.lastname: Delbrel
authors.affiliation: Department of Hematology, Institut Universitaire du Cancer, Toulouse, France;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hebraud
authors.affiliation: Department of Hematology, Institut Universitaire du Cancer, Toulouse, France;
authors.forename: Murielle
authors.initials: M
authors.lastname: Roussel
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Bordeaux, France;
authors.forename: Gerald
authors.initials: G
authors.lastname: Marit
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire St-Antoine, Paris, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire St-Antoine, Paris, France;
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Department of Hematology, Centre Hospitalier, Perigueux, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Rodon
authors.affiliation: Department of Hematology, Centre Hospitalier, Chalon sur Saone, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Voillat
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Amiens, France;
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Limoges, France;
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Créteil, France;
authors.forename: Karim
authors.initials: K
authors.lastname: Belhadj
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Besançon, France;
authors.forename: Jean
authors.initials: J
authors.lastname: Fontan
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Dijon, France;
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.affiliation: Department of Hematology, Institut Paoli Calmettes, Marseille, France; and.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Stoppa
authors.affiliation: Department of Hematology, Institut Universitaire du Cancer, Toulouse, France;
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Lille, France;
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Unité Mixte de Génomique du Cancer, Centre Hospitalier Universitaire, and INSERM U892, Nantes, France;
authors.forename: Stephane
authors.initials: S
authors.lastname: Minvielle
authors.affiliation: Unit for Genomics in Myeloma, Institut Universitaire du Cancer-Oncopole, and Centre de Recherches sur le Cancer de Toulouse INSERM 1037, Toulouse, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D014178:Translocation, Genetic; D014314:Trisomy / Q000235:genetics*