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Myeloma

Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma

Leukemia volume 24, pages 833–842 (2010)Cite this article

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Abstract

In this study, we correlated array-comparative genomic hybridization-defined abnormalities with survival in two different cohorts of patients treated with therapy based on high-dose melphalan with autologous stem-cell transplantation (64 from the Mayo Clinic and 67 from the University of Arkansas Medical School) and identified that several regions of genomic gains and losses were significantly associated with poorer survival. Three noncontiguous survival relevant regions covering 1p31-33 and two noncontiguous regions covering 20p12.3-12.1 were common between the two datasets. The prognostic relevance of these hotspots was validated in an independent cohort using fluorescent in situ hybridization, which showed that 1p31-32 loss is significantly associated with shorter survival (24.5 months versus 40 months, log-rank P-value=0.01), whereas 20p12 loss has a trend toward shorter survival (26.3 months versus 40 months, log-rank P-value=0.06). On multivariate analysis, 1p31-32 loss is an independent prognostic factor. On further analysis, the prognostic impact of 1p31-32 loss is due to shortening of post-relapse survival as there is no impact on complete response rates and progression-free survival.

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Acknowledgements

RF is a Clinical Investigator of the Damon Runyon Cancer Research Fund and is a Clinical Investigator at the Mayo Clinic. WJC is supported by NMRC Clinician Scientist Investigator award. JJK is supported by the Gene and Mary Lou Kurtz Fellowship in Multiple Myeloma Research. RF is also supported in part by the Donaldson Charitable fund Trust, grants R01 CA83724-01, SPORE P50, CA100707-01, and P01 CA62242 from the National Cancer Institute. Dr Fonseca is also supported by the grant CA015083 from the National Cancer Institute.

Author's Contribution

Wee J Chng performed experimental analysis and wrote the manuscript. Tae-Hoon Chung performed the data analysis. Scott Van Wier performed FISH experiments. Jonathan J Keats performed aCGH experiments. Angela Baker performed aCGH experiments. P Leif Bergsagel designed the study and approved the manuscript. Morie A Gertz contributed the validation dataset and performed the analysis. John Carpten designed the study and approved the manuscript. Rafael Fonseca designed the study and wrote the manuscript.

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Author notes

  1. W J Chng, M A Gertz and T-H Chung: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, USA

    W J Chng, S Van Wier, J J Keats, P L Bergsagel & R Fonseca

  2. Department of Haematology-Oncology, National University Health System, National University of Singapore, Singapore

    W J Chng

  3. Cancer Science Institute of Singapore, National University of Singapore, Singapore

    W J Chng

  4. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    M A Gertz

  5. TGen, Phoenix, AZ, USA

    T-H Chung, A Baker & J Carpten

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Correspondence to R Fonseca.

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Chng, W., Gertz, M., Chung, TH. et al. Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma. Leukemia 24, 833–842 (2010). https://doi.org/10.1038/leu.2010.21

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