title: Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling.
abstract: Hyperdiploid multiple myeloma (H-MM) is the most common form of myeloma. In this gene expression profiling study, we show that H-MM is defined by a protein biosynthesis signature that is primarily driven by a gene dosage mechanism as a result of trisomic chromosomes. Within H-MM, four independently validated patient clusters overexpressing nonoverlapping sets of genes that form cognate pathways/networks that have potential biological importance in multiple myeloma were identified. One prominent cluster, cluster 1, is characterized by high expression of cancer testis antigen and proliferation-associated genes. Tumors from these patients were more proliferative than tumors in other clusters (median plasma cell labeling index, 3.8; P < 0.05). Another cluster, cluster 3, is characterized by genes involved in tumor necrosis factor/nuclear factor-kappaB signaling and antiapoptosis. These patients have better response to bortezomib as compared with patients within other clusters (70% versus 29%; P = 0.02). Furthermore, for a group of patients generally thought to have better prognosis, a cluster of patients with short survival (cluster 1; median survival, 27 months) could be identified. This analysis illustrates the heterogeneity within H-MM and the importance of defining specific cytogenetic prognostic factors. Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients.
authors.affiliation: Department of Hematology-Oncology, Mayo Clinic, Scottsdale, Arizona, USA. Chng.wee@mayo.edu
authors.forename: Wee J
authors.initials: WJ
authors.lastname: Chng
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.forename: Scott
authors.initials: S
authors.lastname: Vanwier
authors.forename: Greg
authors.initials: G
authors.lastname: Ahmann
authors.forename: Tammy
authors.initials: T
authors.lastname: Price-Troska
authors.forename: Kim
authors.initials: K
authors.lastname: Henderson
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Chung
authors.forename: Seungchan
authors.initials: S
authors.lastname: Kim
authors.forename: George
authors.initials: G
authors.lastname: Mulligan
authors.forename: Barbara
authors.initials: B
authors.lastname: Bryant
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.forename: Morie
authors.initials: M
authors.lastname: Gertz
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Martha
authors.initials: M
authors.lastname: Lacy
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Robert
authors.initials: R
authors.lastname: Kyle
authors.forename: Philip
authors.initials: P
authors.lastname: Greipp
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D015331:Cohort Studies; D003907:Dexamethasone / Q000627:therapeutic use; D004171:Diploidy; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D005810:Multigene Family; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D014176:Protein Biosynthesis / Q000235:genetics; D011719:Pyrazines / Q000627:therapeutic use; D014314:Trisomy
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone