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Cited by 637Multiple Myeloma Research and TreatmentsLymphoma Diagnosis and TreatmentBone Tumor Diagnosis and Treatments

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Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3

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Chesi, Marta, Nardini, Elena, Brents, Leslie A., Schröck, Evelin, Ried, Thomas, Kuehl, W. Michael, Bergsagel, P. Leif·1997·Nature Genetics
DOI 10.1038/ng0797-260PMC PMC3901950
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Abstract

Dysregulation of oncogenes by translocation to the IgH locus (14q32) is a seminal event in the pathogenesis of B-cell tumours. In multiple myeloma (MM), translocations to the IgH locus have been reported at an incidence of 20-60%. For most translocations, the partner chromosome is unknown (14q+); for the others, a diverse array of chromosomal partners have been identified, with 11q13 (cyclin D1) the only chromosome that is frequently involved. Recently, we developed a Southern-blot assay that detects translocation breakpoint fragments in most MM tumours, including those with no translocation detected by conventional karyotyping. In a continuing analysis of translocation in 21 myeloma cell lines and primary tumours, we show that the novel, karyotypically silent translocation t(4;14)(p16.3;q32.3) is present in five lines and at least three of ten primary tumours. The chromosome-4 breakpoints are clustered in a 70-kb region centromeric to the fibroblast growth factor receptor 3 gene (FGFR3), the apparent dysregulated oncogene. Two lines and one primary tumour with this translocation selectively express an FGFR3 allele containing activating mutations identified previously in thanatophoric dwarfism. We propose that after the t(4;14) translocation, somatic mutation during tumour progression frequently generates in FGFR3 protein that is active in the absence of ligand.

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Research works printed but not linked: 31

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Metadata

Authors
Chesi, M., Nardini, E., Brents, L. A., Schröck, E., Ried, T., Kuehl, W. M., & Bergsagel, P. L.
Affiliations
  • National Institutes of Health (US)
  • Cornell University (US)
Corresponding author
Kuehl, W. Michael
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
1997-07
Volume
16
Issue
3
Pages
260-264
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng0797-260
PMC
PMC3901950
OpenAlex
W2054290966
Cited by
637
References
0
Citations by year
2026: 4 · 2025: 3 · 2024: 13 · 2023: 14 · 2022: 11 · 2021: 11 · 2020: 14 · 2019: 16 · 2018: 13 · 2017: 13 · 2016: 19 · 2015: 15 · 2014: 23 · 2013: 21 · 2012: 26
FWCI
17.29
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (K01CA074265)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone Tumor Diagnosis and Treatments
Keywords
multiple myeloma, FGFR3, activating mutations, somatic mutations, myeloma cell lines, thanatophoric dwarfism
MeSH terms
Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 4, Humans, Karyotyping, Molecular Sequence Data, Multiple Myeloma, Mutation, Oncogenes, Protein-Tyrosine Kinases, RNA, Messenger, Translocation, Genetic, Tumor Cells, Cultured, Blotting, Southern, Immunoblotting, Blotting, Northern, DNA Probes, Gene Expression Regulation, Neoplastic, Polymerase Chain Reaction, In Situ Hybridization, Fluorescence, Receptors, Fibroblast Growth Factor, Receptor, Fibroblast Growth Factor, Type 3

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