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Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations

From the Molecular Cytogenetics Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain (CL, SA, JS, BF, DB, JCC); Department of Genetics, University of Navarra, Pamplona, Navarra, Spain (BS, MJC); Area of Cancer, Area of Cell Therapy and Haematology Service, University Clinic, University of Navarra and Foundation for Applied Medical Research, Pamplona, Navarra, Spain (FP)

Correspondence: Juan C. Cigudosa, PhD, Molecular Cytogenetics Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain. E-mail address: jccigudosa{at}cnio.es

Background and Objectives: Multiple myeloma (MM) is a malignant plasma cell neoplasia in which genetic studies have shown that genomic changes may affect almost all chromosomes, as shown by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Our objective was the genomic characterization of CD 138 positive primary MM samples by means of a high resolution array CGH platform.

Design and Methods: For the first time, a high resolution array CGH with more than 40,000 probes, has been used to analyze 26 primary MM samples after the enrichment of CD138-positive plasma cells.

Results: This approach identified copy number imbalances in all cases. Bioinformatics strategies were optimized to perform data analysis allowing the segregation of hyperdiploid and non-hyperdiploid cases by array CGH. Additional analysis showed that structural chromosome rearrangements were more frequently seen in hyperdiploid cases. We also identified the same Xq21 duplication in nearly 20% of the cases, which originated through unbalanced chromosome translocations. High level amplifications and homozygous deletions were recurrently observed in our series and involved genes with meaningful function in cancer biology.

Interpretation and Conclusions: High resolution array CGH allowed us to identify copy number changes in 100% of the primary MM samples. We segregated different MM subgroups based on their genomic profiles which made it possible to identify homozygous deletions and amplifications of great genetic relevance in MM.

Key words: multiple myeloma, arrayCGH, hyperdiploid, amplification, homozygous deletion.

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