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

✍ Scribed by Sonia Fabris; Katia Todoerti; Laura Mosca; Luca Agnelli; Daniela Intini; Marta Lionetti; Silvana Guerneri; Giorgio Lambertenghi-Deliliers; Francesco Bertoni; Antonino Neri

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
427 KB
Volume
46
Category
Article
ISSN
1045-2257

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✦ Synopsis

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 ∼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. © 2007 Wiley‐Liss, Inc.

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