FGFR3 and/or MMSET activation in a subset of MM is associated with the presence of the t(4;14)(p16;q32).
(A) A bar graph of normalized mRNA expression levels forFGFR3 (▪) and/or MMSET (▨) from CD138-enriched PCs from 32 MM cases. The gene expression signal (a quantitative value of gene expression derived from fluorescence intensity of cRNA hybridization derived from Affymetrix microarray hybridization) is on the vertical axis and samples are on the horizontal axis. The samples are ordered from left to right based on increasing level of expression of FGFR3. (B) A total of 14 MM samples, 9 with MMSET expression but lackingFGFR3 (MMSET+/FGFR3−) and 5 lacking expression of both, (MMSET−/FGFR3−) as observed in microarray experiments, were analyzed for the presence of the t(4;14)(p16;q32) translocation–specific IGHJH2/FMMSET fusion transcript. There were 8 MMSET+/FGFR3− samples positive for the fusion transcript. The size of the PCR product is dependent on the breakpoint position. One MMSET+/FGFR3− case, (P084), negative for both JH1 and JH2 fusion transcripts, was confirmed to have the t(4;14)(p16;q32) by FISH. All 5 MMSET−/FGFR3−cases were negative for the fusion transcript. Previous studies have shown that FGFR3 spike cases exhibit fusion transcripts.3 A negative control (H2O) and positive control (human MM cell line H929) are located to the right. The 123–base pair DNA molecular-weight size standard is to the left.
