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Myeloma

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

Leukemia volume 26, pages 2521–2529 (2012)Cite this article

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Abstract

Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

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Acknowledgements

This work was partially supported by Spanish FIS (PI080568 and PS0901897), the Spanish Myeloma Network Program (RD06/0020/0006) and the ‘Gerencia Regional de Salud, Junta de Castilla y León’ (GRS 702/A/11) grant. MES is supported by the Ministerio de Sanidad y Consumo (CA08/00212). We thank ‘Grupo Español de Mieloma’ clinicians for providing MM samples and S González, I Rodriguez, I Isidro, T Prieto y V Gutierrez for technical assistance.

AUTHOR CONTRIBUTIONS

LLC and MES participated in the design of the study, carried out all molecular studies, prepared the database for the final analysis and prepared the initial version of the paper. SB participated in the analysis of the study and provided preapproval of the final version of the paper. RG-S, MG and MVM participated in the design of the study and supervised the statistical analysis of the study. LAC and JMS participated in the statistical analysis of the study. EMG provided technical assistance. JB, AO, MH-G, PG and JH are clinicians who contributed to collection samples. JMH-R participated in the design of the study and provided the FISH results. JFSM and NCG were the initial persons promoting the study. They were responsible for the overall group and for the most important revision of the draft, as well as the persons who gave their final approval of the version to be published.

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Author notes

  1. L López-Corral and M E Sarasquete: These authors contributed equally to this work.

Authors and Affiliations

  1. Servicio de Hematología del Hospital Universitario de Salamanca, IBMCC (USAL-CSIC) e IBSAL, Salamanca, Spain

    L López-Corral, M E Sarasquete, R García-Sanz, M V Mateos, L A Corchete, M González, J M Hernández-Rivas, J F San Miguel & N C Gutiérrez

  2. Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clinic, Universitat de Barcelona, IDIBAPS, Barcelona, Spain

    S Beà

  3. Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain

    J M Sayagués & E M García

  4. Servicio de Hematología de Hospital Clinic, IDIBAPS, Barcelona, Spain

    J Bladé

  5. Servicio de Hematología de Hospital Germans Trias I Pujol, Badalona, Spain

    A Oriol

  6. Servicio de Hematología de Hospital Universitario de Canarias, Tenerife, Spain

    M T Hernández-García

  7. Servicio de Hematología de Hospital Universitario Miguel Servet, Zaragoza, Spain

    P Giraldo

  8. Servicio de Hematología de Hospital General de Segovia, Segovia, Spain

    J Hernández

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  1. L López-Corral
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Correspondence to N C Gutiérrez.

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López-Corral, L., Sarasquete, M., Beà, S. et al. SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status. Leukemia 26, 2521–2529 (2012). https://doi.org/10.1038/leu.2012.128

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