Mutation, SNP, and isoform analysis of fibroblast growth factor receptor 3 (FGFR3) in 150 newly diagnosed multiple myeloma patients

The t(4;14) translocation in multiple myeloma (MM) is identified in ∼15% of patient samples, dysregulating FGFR3 and MMSET. Activating FGFR3 mutations are observed in myeloma cell lines and in late stage MM but the incidence of mutation in newly diagnosed patient samples is unknown. Gene expression profiling of 150 newly diagnosed patients revealed FGFR3 over-expression in 24 (16%). RT-PCR and FISH confirmed that all of the FGFR3 positive patients carried the t(4;14) translocation. Sequencing of the entire open reading frame of FGFR3 gene identified an insertion of two amino acids in one patient and a Y241C point mutation in another. Moreover, two isoforms of FGFR3 that have not previously been described in MM were identified. Furthermore, we identified the C294T polymorphism in 17 of 22 patient samples. Therefore mutations of FGFR3 occur in less than 5% of t(4;14) positive and in less than 1% of newly diagnosed myeloma patients overall.