FGFR3 dysregulation in multiple myeloma: frequency and prognostic relevance

Abstract

Summary. The t(4:14) translocation affects two potential oncogenes, FGFR3 and MMSET, in multiple myeloma (MM). We investigated the frequency of FGFR3 dysregulation and its prognostic value in MM. FGFR3 mRNA levels were determined in 110 diagnostic bone marrow (BM) samples from MM patients. In addition, selected BM samples were screened for elevated MMSET mRNA levels. 14AE5% (16/110) of MM BM samples showed dysregulated FGFR3 expression.Follow-up of 76 MM patients showed no significant difference between FGFR3 dysfunction and survival (P ¼ 0AE3) or correlation with known prognostic factors. Further, no linear relation was observed between FGFR3 and MMSET levels.

Plasma exchange as a source of protein c for acute‐onset protein c pathway failure

“…Consistent with their results, Rasmussen et al (2002) also suggested that t(4;14)(p16.3;q32) is a monoclonal gammopathy of uncertain significance (MGUS)-to-myeloma transition event rather than a primary event, citing as support the lower prevalence of t(4;14)(p16.3;q32) in MGUS compared with multiple myeloma in some studies (Avet-Loiseau et al, 2002). This latter point is still controversial, as we have demonstrated a similar incidence of t(4;14)(p16.3;q32) in MGUS and myeloma using interphase FISH; it is, therefore, not clear that this abnormality represents a progression event.…”

“…Such a test would also allow the routine assessment of the antiplatelet effect of other drugs, like antihypertensives (e.g. in the studies cited by Endler et al, 2002) and lipid-lowering drugs (Milionis et al, 1999 Rasmussen et al (2002), showing no correlation between FGFR3 overexpression and clinical outcome in myeloma. This was surprising, as we have recently demonstrated by cytoplasmic immunoglobulin fluorescence in situ hybridization (cIg-FISH) a significantly shorter survival (26 vs 45 months, P < 0AE001) in myeloma patients having t(4;14) (p16.3;q32), (Fonseca et al, 2001).…”

“…However, to date the only reported mechanism of FGFR3 dysregulation in multiple myeloma (MM) is by t(4;14) and only a single case of t(4;14) without FGFR3 dysregulation has been reported (Nakazawa et al, 2000). In addition, in our study, mRNA from 7 ⁄ 16 FGFR3-positive MM patients was available for analysis of MMSET dysregulation, showing MMSET dysregulation in 7 ⁄ 7 patients (Rasmussen et al, 2002). The good correlation between t(4;14) and FGFR3 dysregulation and the fact that all tested FGFR3-positive patients simultaneously showed MMSET dysregulation suggest that it is unlikely that the use of FGFR3 dysregulation as a surrogate marker for t(4;14) is the explanation for the discrepancy between the study reported by Fonseca et al (2001a) and our results (Rasmussen et al, 2002).…”

“…In addition, in our study, mRNA from 7 ⁄ 16 FGFR3-positive MM patients was available for analysis of MMSET dysregulation, showing MMSET dysregulation in 7 ⁄ 7 patients (Rasmussen et al, 2002). The good correlation between t(4;14) and FGFR3 dysregulation and the fact that all tested FGFR3-positive patients simultaneously showed MMSET dysregulation suggest that it is unlikely that the use of FGFR3 dysregulation as a surrogate marker for t(4;14) is the explanation for the discrepancy between the study reported by Fonseca et al (2001a) and our results (Rasmussen et al, 2002). The discrepancy may originate from the low number of FGFR3-positive MM patients included in the clinical follow-up and ⁄ or it may illustrate that, to understand the clinical outcome of the t(4;14) subgroup of patients, both the mutational status of FGFR3 (Chesi et al, 2001) and presence of D13 (Fonseca et al, 2001b;Avet-Loiseau et al, 2002) need to be assessed at time of diagnosis.…”

Quick detection of overexpressed genes caused by myeloma-specific chromosomal translocations using multiplex RT-PCR

“…However, the specific clinical features of MM caused by individual chromosomal translocations and overexpressed genes are unclear. On the other hand, clinical observations have indicated that MM patients with t(11;14)(q13;q32) and translocation of CCND1 show a better prognosis (17)(18)(19), while MM patients with t(4;14)(q32.3;q32) and FGFR3 overexpression have a worse prognosis (20)(21)(22)(23).…”