A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains anIGH/MMSET fusion transcript
M Santra, F Zhan, E Tian, B Barlogie… - Blood, The Journal …, 2003 - ashpublications.org
M Santra, F Zhan, E Tian, B Barlogie, J Shaughnessy Jr
Blood, The Journal of the American Society of Hematology, 2003•ashpublications.orgPrevious studies have revealed that that approximately 10% to 15% of multiple myelomas
(MMs) are characterized by a reciprocal t (4; 14)(p16; q32) translocation that activates
expression of FGFR3 and creates an IGH/MMSET fusion transcript. Current data suggest
that activation of FGFR3 is the oncogenic consequence of this rearrangement. Using a
combination of microarray profiling, reverse transcriptase–polymerase chain reaction (RT-
PCR), and interphase fluorescence in situ hybridization (FISH), we show that 32 (18%) of …
(MMs) are characterized by a reciprocal t (4; 14)(p16; q32) translocation that activates
expression of FGFR3 and creates an IGH/MMSET fusion transcript. Current data suggest
that activation of FGFR3 is the oncogenic consequence of this rearrangement. Using a
combination of microarray profiling, reverse transcriptase–polymerase chain reaction (RT-
PCR), and interphase fluorescence in situ hybridization (FISH), we show that 32 (18%) of …
Previous studies have revealed that that approximately 10% to 15% of multiple myelomas (MMs) are characterized by a reciprocal t(4;14)(p16;q32) translocation that activates expression ofFGFR3 and creates an IGH/MMSET fusion transcript. Current data suggest that activation of FGFR3is the oncogenic consequence of this rearrangement. Using a combination of microarray profiling, reverse transcriptase–polymerase chain reaction (RT-PCR), and interphase fluorescence in situ hybridization (FISH), we show that 32 (18%) of 178 newly diagnosed cases of MM harbor the t(4;14)(p16;q32). Importantly, 32% of these cases lack expression of FGFR3, yet express MMSET and have an IGH/MMSET fusion transcript. Interphase FISH showed that whereas the IGH/MMSET fusion was present in more than 80% of the clonotypic plasma cells in these novel cases, there was typically a complete loss of one copy of FGFR3. These data indicate that the t(4;14)(p16;q32) and loss of FGFR3occurred at a very early stage and suggest that activation ofMMSET, not FGFR3, may be the critical transforming event of this recurrent translocation.
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