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.
Molecular and transcriptional characterization of the novel 17p11.2-p12 amplicon in multiple myeloma / S. Fabris, K. Todoerti, L. Mosca, L. Agnelli, D. Intini, M. Lionetti, S. Guerneri, G. Lambertenghi-Deliliers, F. Bertoni, A. Neri. - In: GENES, CHROMOSOMES & CANCER. - ISSN 1045-2257. - 46:12(2007 Dec), pp. 1109-1118.
|Titolo:||Molecular and transcriptional characterization of the novel 17p11.2-p12 amplicon in multiple myeloma|
FABRIS, SONIA (Primo)
TODOERTI, KATIA (Secondo)
NERI, ANTONINO (Ultimo)
|Parole Chiave:||Gene Expression Profiling ; Chromosomes, Human, Pair 17 ; Base Sequence ; Models, Genetic ; Humans ; Molecular Sequence Data ; In Situ Hybridization, Fluorescence ; Cell Line, Tumor ; Transcription, Genetic ; Multiple Myeloma ; Gene Amplification|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||dic-2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/gcc.20494|
|Appare nelle tipologie:||01 - Articolo su periodico|