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Molecular and transcriptional characterization of the novel 17p11.2‐p12 amplicon in multiple myeloma
Author(s) -
Fabris Sonia,
Todoerti Katia,
Mosca Laura,
Agnelli Luca,
Intini Daniela,
Lionetti Marta,
Guerneri Silvana,
LambertenghiDeliliers Giorgio,
Bertoni Francesco,
Neri Antonino
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20494
Subject(s) - amplicon , gene duplication , biology , comparative genomic hybridization , fluorescence in situ hybridization , multiple myeloma , microbiology and biotechnology , plasma cell dyscrasia , gene , locus (genetics) , cancer research , multiplex ligation dependent probe amplification , genetics , genome , antibody , polymerase chain reaction , chromosome , exon , immunology , immunoglobulin light chain
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.