Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types. PLoS One 2015;10(5):e0127828
Date
05/29/2015Pubmed ID
26020268Pubmed Central ID
PMC4447437DOI
10.1371/journal.pone.0127828Scopus ID
2-s2.0-84932602156 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
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.
Author List
Amend SR, Wilson WC, Chu L, Lu L, Liu P, Serie D, Su X, Xu Y, Wang D, Gramolini A, Wen XY, O'Neal J, Hurchla M, Vachon CM, Colditz G, Vij R, Weilbaecher KN, Tomasson MHMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Vesicular TransportAnimals
B-Lymphocytes
Bone Marrow Cells
Genome-Wide Association Study
Humans
Macrophages
Mice
Multiple Myeloma
Neoplasm Proteins
Point Mutation
Polymorphism, Single Nucleotide
Receptors, Tumor Necrosis Factor
Stromal Cells
