Whole genome sequence of multiple myeloma-prone C57BL/KaLwRij mouse strain suggests the origin of disease involves multiple cell types

Sarah R. Amend, William C. Wilson, Liang Chu, Lan Lu, Pengyuan Liu, Daniel Serie, Xinming Su, Yalin Xu, Dingyan Wang, Anthony Gramolini, Xiao Yan Wen, Julie O'Neal, Michelle Hurchla, Celine M Vachon, Graham Colditz, Ravi Vij, Katherine N. Weilbaecher, Michael H. Tomasson

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is the requisite precursor to multiple myeloma (MM), a malignancy of antibody-producing plasma B-cells. The genetic basis of MGUS and its progression to MM remains poorly understood. C57BL/KaLwRij (KaLwRij) is a spontaneously-derived inbred mouse strain with a high frequency of benign idiopathic paraproteinemia (BIP), a phenotype with similarities to MGUS including progression to MM. Using mouse haplotype analysis, human MM SNP array data, and whole exome and whole genome sequencing of KaLwRij mice, we identified novel KaLwRij gene variants, including deletion of Samsn1 and deleterious point mutations in Tnfrsf22 and Tnfrsf23. These variants significantly affected multiple cell types implicated in MM pathogenesis including B-cells, macrophages, and bone marrow stromal cells. These data demonstrate that multiple cell types contribute to MM development prior to the acquisition of somatic driver mutations in KaLwRij mice, and suggest that MM may an inherently non-cell autonomous malignancy.

Original languageEnglish (US)
Article numbere0127828
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 28 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Amend, S. R., Wilson, W. C., Chu, L., Lu, L., Liu, P., Serie, D., Su, X., Xu, Y., Wang, D., Gramolini, A., Wen, X. Y., O'Neal, J., Hurchla, M., Vachon, C. M., Colditz, G., Vij, R., Weilbaecher, K. N., & Tomasson, M. H. (2015). Whole genome sequence of multiple myeloma-prone C57BL/KaLwRij mouse strain suggests the origin of disease involves multiple cell types. PLoS One, 10(5), [e0127828]. https://doi.org/10.1371/journal.pone.0127828