title: The enigma of ectopic expression of FGFR3 in multiple myeloma: a critical initiating event or just a target for mutational activation during tumor progression.
abstract: The t(4;14)(p16.3;q32) translocation that occurs uniquely in a subset of multiple myeloma tumors results in ectopic expression of wild-type FGFR3 and enhanced expression of MMSET, a gene that is homologous to the MLL gene that is involved in acute myeloid leukemias. Wild-type FGFR3 appears to be weakly transforming in a hematopoietic murine model, whereas FGFR3 that contains kinase-activating mutations is strongly transforming in NIH3T3 cells and the hematopoietic model. The subsequent acquisition of FGFR3 kinase-activating mutations in some tumors with t(4;14) translocations confirms a role for FGFR3 in tumor progression. However, it remains to be proven if and how dysregulation of FGFR3 or MMSET mediates an early oncogenic process in multiple myeloma.
authors.affiliation: Weill Medical College of Cornell University, New York, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Chesi
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.forename: W Michael
authors.initials: WM
authors.lastname: Kuehl
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3