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Common genetic variants in 11q13.3 and 9q22.33 are associated with molecular subgroups of multiple myeloma

Leukemia volume 29, pages 2418–2421 (2015)Cite this article

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Recently, Weinhold et al.1 reported the association of a potentially functional single-nucleotide polymorphism (SNP) in the CCND1 gene with an increased incidence of t(11;14) in multiple myeloma (MM). MM can be classified by gene expression profiling (GEP) into seven well-defined molecular subgroups, of which four are strongly influenced by specific translocations involving the immunoglobulin heavy chain locus.2 These translocations are characterized by transcriptional activation of the genes CCND1 [t(11;14)(q13;q32)], CCND3 [t(6;14)(p21;q32)], c-MAF [t(14;16)(q32;q23)], MAFB [t(14;20)(q32;q11)] and FGFR3/MMSET [t(4;14)(q16;q32)]. Specific cytogenetic abnormalities normally assessed by fluorescence in situ hybridization, including these immunoglobulin heavy chain translocations, can be predicted with high accuracy by spiked gene expression levels with a technique known as virtual karyotyping.3, 4 In the present study, we investigate whether SNPs previously associated with overall risk of MM5, 6, 7 and t(11;14)1 are associated with any disease-specific subset. We also performed genome-wide scans of associations between common genetic variants to molecular subgroups.

Genotypes at 777 681 SNPs in a discovery set of 972 newly diagnosed MM patients of European ancestry and 1064 cancer-free controls, plus a replication set of 252 more recent European ancestry patients genotyped at selected SNPs, form the basis of this analysis.7 The study was conducted under the auspices of the Institutional Review Board at the University of Arkansas for Medical Sciences. Gene expression profiling from CD138-selected plasma cells from these patients within 3 months before treatment8 was available for 650 patients in the discovery set and for all 252 patients in the replication set. Patients included in specific MM subgroups served as cases and were compared with 1064 non-cancer controls. The results of this analysis showed that one SNP was significantly associated with Cyclin D1 spiked expression (CCND1-hi) and one SNP was significantly associated with the proliferation (PR) subgroup (Table S1).

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Acknowledgements

This study received financial support from the National Institutes of Health (NIH)/National Institute of Nursing Research (NINR) 5RC2NR011945 as primary support, UAMS Translational Research Institute at University of Arkansas for Medical Sciences (UAMS; grant 1UL1RR029884), the Elizabeth Stanley Cooper Chair in Oncology Nursing, the Research Fund at Region Sjaelland, Denmark, the Danish Cancer Society, Denmark; Familien Hede Nielsens Fund, Denmark; the Dagmar Marshall fund, Denmark, and the UAMS Medical Research Foundation.

Author contributions

SWE, CJH and AJV conceived and designed the research, interpreted results and wrote the manuscript. OWS and SWC collected and verified clinical and gene expression profiling data. SWE performed the statistical analysis. ET, JE and BB interpreted results and edited the manuscript.

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Authors and Affiliations

  1. Genetic Epidemiology and Omics Research, Research Triangle Park, NC, USA,

    S W Erickson

  2. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA,

    O W Stephens, S S Chavan, E Tian, J Epstein, B Barlogie & C J Heuck

  3. Department of Hematology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark,

    A J Vangsted

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  1. S W Erickson
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  2. O W Stephens
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  3. S S Chavan
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  6. B Barlogie
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  7. C J Heuck
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  8. A J Vangsted
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Corresponding author

Correspondence to A J Vangsted.

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The authors declare no conflict of interest.

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Erickson, S., Stephens, O., Chavan, S. et al. Common genetic variants in 11q13.3 and 9q22.33 are associated with molecular subgroups of multiple myeloma. Leukemia 29, 2418–2421 (2015). https://doi.org/10.1038/leu.2015.238

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