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  • Original Article
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Myeloma

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

Abstract

In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Δ13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Δ13, p53 deletion or t(4;14) was present, but only Δ13 remained significant on multivariate analysis. Patients with Δ13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Δ13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Δ13 disappeared; their outcome matched that of patients with no detectable Δ13 (P=0.115). Addition of ploidy status to iFISH-Δ13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Δ13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Δ13. We conclude that Δ13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Δ13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

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References

  1. Debes-Marun CS, Dewald GW, Bryant S, Picken E, Santana-Davila R, Gonzalez-Paz N et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia 2003; 17: 427–436.

    Article  CAS  PubMed  Google Scholar 

  2. Kuehl WM, Bergsagel PL . Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002; 2: 175–187.

    Article  CAS  PubMed  Google Scholar 

  3. Avet-Loiseau H, Facon T, Grosbois B, Magrangeas F, Rapp MJ, Harousseau JL et al. Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation. Blood 2002; 99: 2185–2191.

    Article  CAS  PubMed  Google Scholar 

  4. Hideshima T, Bergsagel PL, Kuehl WM, Anderson KC . Advances in biology of multiple myeloma: clinical applications. Blood 2004; 104: 607–618.

    Article  CAS  PubMed  Google Scholar 

  5. Fonseca R, Debes-Marun CS, Picken EB, Dewald GW, Bryant SC, Winkler JM et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 2003; 102: 2562–2567.

    Article  CAS  PubMed  Google Scholar 

  6. Tricot G, Barlogie B, Jagannath S, Bracy D, Mattox S, Vesole DH et al. Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. Blood 1995; 86: 4250–4256.

    CAS  PubMed  Google Scholar 

  7. Fonseca R, Harrington D, Oken MM, Dewald GW, Bailey RJ, Van Wier SA et al. Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an eastern cooperative oncology group study. Cancer Res 2002; 62: 715–720.

    CAS  PubMed  Google Scholar 

  8. Facon T, Avet-Loiseau H, Guillerm G, Moreau P, Genevieve F, Zandecki M et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001; 97: 1566–1571.

    Article  CAS  PubMed  Google Scholar 

  9. Desikan R, Barlogie B, Sawyer J, Ayers D, Tricot G, Badros A et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000; 95: 4008–4010.

    CAS  PubMed  Google Scholar 

  10. Shaughnessy J, Jacobson J, Sawyer J, McCoy J, Fassas A, Zhan F et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with total therapy I: interpretation in the context of global gene expression. Blood 2003; 101: 3849–3856.

    Article  CAS  PubMed  Google Scholar 

  11. Zojer N, Konigsberg R, Ackermann J, Fritz E, Dallinger S, Kromer E et al. Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization. Blood 2000; 95: 1925–1930.

    CAS  PubMed  Google Scholar 

  12. Avet-Louseau H, Daviet A, Sauner S, Bataille R . Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13. Br J Haematol 2000; 111: 1116–1117.

    Article  CAS  PubMed  Google Scholar 

  13. Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64: 1546–1558.

    Article  CAS  PubMed  Google Scholar 

  14. Avet-Loiseau H, Li JY, Morineau N, Facon T, Brigaudeau C, Harousseau JL et al. Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma. Intergroupe Francophone du Myelome. Blood 1999; 94: 2583–2589.

    CAS  PubMed  Google Scholar 

  15. Kaufmann H, Kromer E, Nosslinger T, Weltermann A, Ackermann J, Reisner R et al. Both chromosome 13 abnormalities by metaphase cytogenetics and deletion of 13q by interphase FISH only are prognostically relevant in multiple myeloma. Eur J Haematol 2003; 71: 179–183.

    Article  CAS  PubMed  Google Scholar 

  16. Shaughnessy Jr J, Tian E, Sawyer J, McCoy J, Tricot G, Jacobson J et al. Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II. Br J Haematol 2003; 120: 44–52.

    Article  PubMed  Google Scholar 

  17. Dewald G, Therneau T, Larson D, Lee YK, Fink S, Smoley S et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood 2005; 106: 3553–3558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ross FM, Ibrahim AH, Vilain-Holmes A, Winfield MO, Chiecchio L, Protheroe RK et al. Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma. Leukemia 2005; 19: 1634–1642.

    Article  CAS  PubMed  Google Scholar 

  19. Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2004; 5: 285.

    Article  Google Scholar 

  20. Wuilleme S, Robillard N, Lode L, Magrangeas F, Beris H, Harousseau JL et al. Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma. Leukemia 2005; 19: 275–278.

    Article  CAS  PubMed  Google Scholar 

  21. Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C . Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 2001; 98: 2229–2238.

    Article  CAS  PubMed  Google Scholar 

  22. Fassas AB, Spencer T, Sawyer J, Zangari M, Lee CK, Anaissie E et al. Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma. Br J Haematol 2002; 118: 1041–1047.

    Article  CAS  PubMed  Google Scholar 

  23. Barlogie B, Alexanian R, Dixon D, Smith L, Smallwood L, Delasalle K . Prognostic implications of tumor cell DNA and RNA content in multiple myeloma. Blood 1985; 66: 338–341.

    CAS  PubMed  Google Scholar 

  24. Garcia-Sanz R, Orfao A, Gonzalez M, Moro MJ, Hernandez JM, Ortega F et al. Prognostic implications of DNA aneuploidy in 156 untreated multiple myeloma patients. Castelano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies. Br J Haematol 1995; 90: 106–112.

    Article  CAS  PubMed  Google Scholar 

  25. Sawyer JR, Waldron JA, Jagannath S, Barlogie B . Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genet Cytogenet 1995; 82: 41–49.

    Article  CAS  PubMed  Google Scholar 

  26. Fassas AB, Tricot G . Chromosome 13 deletion/hypodiploidy and prognosis in multiple myeloma patients. Leuk Lymphoma 2004; 45: 1083–1091.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Leukaemia Research for funding this work. We thank Paul Strike of the Salisbury District Hospital Research and Development Support Unit for help with the statistical analysis, Anthony Moorman for helpful discussions and Andy Rawstron and Roger Owen from the Haematological Malignancy Diagnostic Unit in Leeds for information helpful towards making the diagnosis in some patients. Laura Chiecchio performed research, analysed data and wrote the first draft of the paper; Rebecca KM Protheroe, Ashraf H Ibrahim, Kan Luk Cheung, Christina Rudduck, Gian Paolo Dagrada, Elisabet Dachs Cabanas, Tim Parker, Mathew Nightingale and Ashutosh Wechalekar performed research; Kim H Orchard, Christine J Harrison, Nicholas CP Cross and Gareth J Morgan contributed to the analysis of the data; Fiona M Ross designed and performed research, analysed data. All the authors contributed to the final draft of the paper.

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Correspondence to L Chiecchio.

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Chiecchio, L., Protheroe, R., Ibrahim, A. et al. Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia 20, 1610–1617 (2006). https://doi.org/10.1038/sj.leu.2404304

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