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.

Molecular and transcriptional characterization of the novel 17p11.2-p12 amplicon in multiple myeloma

S. Fabris
Primo
;
K. Todoerti
Secondo
;
L. Mosca;L. Agnelli;D. Intini;M. Lionetti;G. Lambertenghi-Deliliers;A. Neri
Ultimo
2007-12

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.
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 MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/206018
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