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Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms.

Leukemia | Jun 10, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20393505

The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (FGFR3) controlled by the 3' immunoglobulin heavy chain enhancer on der(14) and MMSET controlled by the intronic Emu enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated MMSET, about 25% do not express FGFR3. Therefore, the function of dysregulated wild-type (WT) FGFR3 in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT FGFR3 is overexpressed in B lymphoid cells. Although high levels of FGFR3 resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG FGFR3/Myc mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG Myc mice (P=0.006). We conclude that expression of high levels of WT FGFR3 can be oncogenic and cooperate with MYC to generate B lymphoid tumors. This suggests that dysregulated FGFR3 expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.

Pubmed ID: 20393505 RIS Download

Mesh terms: Animals | Blotting, Southern | Blotting, Western | Female | Gene Expression Profiling | Genes, Immunoglobulin | Humans | Immunoenzyme Techniques | Immunophenotyping | Immunoprecipitation | Lymphoma, B-Cell | Male | Mice | Mice, Transgenic | Multiple Myeloma | Oligonucleotide Array Sequence Analysis | Proto-Oncogene Proteins c-myc | RNA, Messenger | Receptor, Fibroblast Growth Factor, Type 3 | Reverse Transcriptase Polymerase Chain Reaction | Tumor Markers, Biological

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Associated grants

  • Agency: NCI NIH HHS, Id: P50CA097274
  • Agency: NCI NIH HHS, Id: R01 CA151354
  • Agency: NCI NIH HHS, Id: R01 CA151354-01
  • Agency: Intramural NIH HHS, Id:

Mouse Genome Informatics (Data, Gene Annotation)

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