title: Molecular and transcriptional characterization of the novel 17p11.2-p12 amplicon in multiple myeloma.
abstract: Multiple myeloma (MM) is a malignancy of clonal bone marrow plasma cells characterized by a high genomic instability increasing with disease progression. We describe here a genomic amplification at 17p11.2-p12, an unstable chromosomal region characterized by a large number of low-copy repeats, which have been proven to mediate deletion and duplication in several genomic disorders and amplifications in solid tumors. An approximately 5 Mb 17p11.2-p12 amplified region was detected in the KMS-26 myeloma cell line by SNP microarray analysis. Further fluorescence in situ hybridization mapping showed two unidentified amplified chromosomes as well as a complex pattern of rearranged chromosomes 17. The analysis of transcriptional profiles in a proprietary database of myeloma cell lines identified 12 significantly overexpressed genes in the KMS-26 amplified region, including TNFRSF13B/TACI, COPS3, and NCOR1. The evaluation of their expression levels in a database including 141 plasma cell dyscrasia primary tumors showed a significant overexpression of at least one gene in 13 patients. FISH analyses of these patients identified one MM carrying a 3.8 Mb amplified region and two MMs with gains specifically involving the TACI locus. Interestingly, the complete inactivation of TP53 at 17p13.1 was found in the KMS-26, whereas a monoallelic loss was identifiable in two of the three patients carrying gain/amplification. Our data suggest that, similarly to solid tumors, amplification/gain of the 17p11.2-p12 region in MM could be mediated by the presence of repeats located in this region and may provide insights for defining novel candidate myeloma-associated genes.
authors.affiliation: Centro di Genetica Molecolare ed Espressione Genica, Fondazione IRCCS Policlinico, Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Intini
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Silvana
authors.initials: S
authors.lastname: Guerneri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lambertenghi-Deliliers
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002886:Chromosomes, Human, Pair 17; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D014158:Transcription, Genetic