Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types

Sarah R Amend; Michael H Tomasson; 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

doi:10.1371/journal.pone.0127828

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Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types

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Peer reviewed

Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types

Sarah R Amend, Michael H Tomasson, William C Wilson, Liang Chu, Lan Lu, Pengyuan Liu, Daniel Serie, Xinming Su, Yalin Xu, Dingyan Wang, …

PloS one, Vol.10(5), pp.e0127828-e0127828

2015

DOI: 10.1371/journal.pone.0127828

PMCID: PMC4447437

PMID: 26020268

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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.

Receptors, Tumor Necrosis Factor - metabolism

Genome-Wide Association Study

Macrophages - pathology

Stromal Cells - pathology

Humans

Stromal Cells - metabolism

Adaptor Proteins, Vesicular Transport - genetics

Bone Marrow Cells - pathology

Multiple Myeloma - metabolism

Neoplasm Proteins - metabolism

Adaptor Proteins, Vesicular Transport - metabolism

Point Mutation

Macrophages - metabolism

Multiple Myeloma - pathology

Animals

Mice

Polymorphism, Single Nucleotide

B-Lymphocytes - pathology

Neoplasm Proteins - genetics

B-Lymphocytes - metabolism

Bone Marrow Cells - metabolism

Multiple Myeloma - genetics

Receptors, Tumor Necrosis Factor - genetics

Details

Title: Subtitle: Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types
Creators: Sarah R Amend - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Michael H Tomasson - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
William C Wilson - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Liang Chu - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Lan Lu - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Pengyuan Liu - Medical College of Wisconsin, Milwaukee, WI, United States of America
Daniel Serie - Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN, United States of America
Xinming Su - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Yalin Xu - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Dingyan Wang - Department of Physiology, University of Toronto, Toronto, Canada
Anthony Gramolini - Department of Physiology, University of Toronto, Toronto, Canada
Xiao-Yan Wen - Department of Physiology, University of Toronto, Toronto, Canada
Julie O'Neal - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Michelle Hurchla - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Celine M Vachon - Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN, United States of America
Graham Colditz - Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States of America
Ravi Vij - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Katherine N Weilbaecher - Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.10(5), pp.e0127828-e0127828
DOI: 10.1371/journal.pone.0127828
PMID: 26020268
PMCID: PMC4447437
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: 1F31CA174096-01A1 / NCI NIH HHS R21AG040777 / NIA NIH HHS P30 AR057235 / NIAMS NIH HHS 2P01 CA100730 / NCI NIH HHS R01 CA097250 / NCI NIH HHS R21 AG040777 / NIA NIH HHS P01 CA100730 / NCI NIH HHS F31 CA174096 / NCI NIH HHS T32 CA113275 / NCI NIH HHS
Language: English
Date published: 2015
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094324502771

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