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Transcriptional features of multiple myeloma patients with chromosome 1q gain

Leukemia volume 21, pages 1113–1116 (2007)Cite this article

Abnormalities of chromosome 1 are among the most frequent chromosomal alterations in multiple myeloma (MM), being found in up to 45% of patients.1, 2 It has been reported that the short arm of chromosome 1 is preferentially involved in deletions, whereas the long arm is associated with amplification. The gain of 1q (1q/gain) can occur as isochromosomes, duplications or jumping translocations. It has been widely reported that 1q/gain MM patients are characterized by complex karyotypes and aggressive disease, and a close association with poor-risk genetic features, such as chromosome 13q deletion (Δ13) and the t(4;14) translocation has also been described.1 It has been recently demonstrated that gains/amplification of 1q21 increase as the condition goes from smoldering to overt MM, thus suggesting that these regions contain critical genes for disease progression.2 These findings along with the limited information concerning specific transcriptional profiles prompted us to molecularly characterize 1q/gain MMs by FISH and microarray analyses.

Our study includes a panel of 77 MM patients at diagnosis, whose characteristics have been deposited in National Center for Biotechnology Information's Gene Expression Omnibus (GEO; http://www.ncbi.nlm.mih.gov/geo, accession number GSE6401). Bone marrow plasma cells were purified (>90% in all cases) using CD138-immunomagnetic bead selection and characterized by FISH for the presence of 11 polisomy, the most recurrent IGH translocations, ploidy status, Δ13, and global gene expression profiling using the Affymetrix U133A gene chips, as described previously.3 Patients were then stratified accordingly to the proposed translocation/cyclin D (TC) classification in five groups: TC1 characterized by the t(11;14) or t(6;14) translocations, with the consequent overexpression of either CCND1 or CCND3, and a nonhyperdiploid status; TC2 showing low/moderate levels of the CCND1 gene in the absence of any primary IGH translocations, and a hyperdiploid status; TC3 including tumors that do not fall into any of the other groups, most of which express CCND2; TC4 showing high CCND2 levels and the presence of the t(4;14) translocation and TC5 expressing the highest levels of CCND2 in association with either the t(14;16) or t(14;20) translocation.3

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Acknowledgements

This study was supported by grants from the Associazione Italiana Ricerca sul Cancro (AIRC) (to AN); from the Italian Ministry of University and Research (FIRB RBNE01TZZ8 and RBAU01935A) and the OncoSuisse Collaborative Cancer Research Project OCS 01517–02–2004 (to SB); KT was supported by a fellowship from the Fondazione Italiana Ricerca sul Cancro (FIRC).

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Author notes

  1. S Fabris and D Ronchetti: The first two authors contributed equally to this work

Authors and Affiliations

  1. Centro di Genetica Molecolare ed Espressione Genica, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy

    S Fabris, D Ronchetti, L Agnelli, K Todoerti, L Lombardi & A Neri

  2. Dipartimento di Scienze Mediche, Università degli Studi di Milano, Milan, Italy

    D Ronchetti, L Baldini, K Todoerti, G Lambertenghi-Deliliers & A Neri

  3. U.O. Ematologia, A.O. ‘Annunziata’, Cosenza, Italy

    F Morabito

  4. Dipartimento dei Processi Chimici dell’Ingegneria, Università degli Studi, Padua, Italy

    S Bicciato & D Basso

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  1. S Fabris
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  2. D Ronchetti
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  3. L Agnelli
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  7. D Basso
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  10. G Lambertenghi-Deliliers
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  11. A Neri
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Correspondence to A Neri.

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Fabris, S., Ronchetti, D., Agnelli, L. et al. Transcriptional features of multiple myeloma patients with chromosome 1q gain. Leukemia 21, 1113–1116 (2007). https://doi.org/10.1038/sj.leu.2404616

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