title: Genomic analysis of high-risk smoldering multiple myeloma.
abstract: Smoldering myeloma is an asymptomatic plasma cell dyscrasia with a heterogeneous propensity to progress to active myeloma. In order to investigate the biology of smoldering myeloma patients with high risk of progression, we analyzed the genomic characteristics by FISH, SNP-arrays and gene expression profile of a group of patients with high-risk smoldering myeloma included in a multicenter randomized trial. Chromosomal abnormalities detected by FISH and SNP-arrays at diagnosis were not associated to risk of progression to symptomatic myeloma. However, the overexpression of four SNORD genes (SNORD25, SNORD27, SNORD30 and SNORD31) was correlated with shorter time to progression (P<0.03). When plasma cells from high-risk smoldering patients who progressed to symptomatic myeloma were sequentially analyzed, newly acquired lesions together with an increase in the proportion of plasma cells carrying a given abnormality were observed. These findings suggest that gene expression profiling is a valuable technique to identify smoldering myeloma patients with high risk of progression. (Clinical Trials NCT00443235).
authors.affiliation: Servicio de Hematología del Hospital Universitario de Salamanca y Centro de Investigación del Cáncer-IBMCC (USAl-CIC), Universidad de Salamanca, Salamanca, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: López-Corral
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Luis A
authors.initials: LA
authors.lastname: Corchete
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Sarasquete
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D018450:Disease Progression; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor