PMID- 12433679 OWN - NLM STAT- MEDLINE DCOM- 20030407 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 101 IP - 6 DP - 2003 Mar 15 TI - A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. PG - 2374-6 AB - 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 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 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 FGFR3 occurred at a very early stage and suggest that activation of MMSET, not FGFR3, may be the critical transforming event of this recurrent translocation. FAU - Santra, Madhumita AU - Santra M AD - Donna and Donald Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. FAU - Zhan, Fenghuang AU - Zhan F FAU - Tian, Erming AU - Tian E FAU - Barlogie, Bart AU - Barlogie B FAU - Shaughnessy, John Jr AU - Shaughnessy J Jr LA - eng GR - CA55819/CA/NCI NIH HHS/United States GR - CA97513/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20021114 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (IgH-MMSET fusion protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Fibroblast Growth Factor) RN - EC 2.7.10.1 (FGFR3 protein, human) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3) SB - IM MH - Bone Marrow/chemistry MH - *Chromosomes, Human, Pair 14 MH - *Chromosomes, Human, Pair 4 MH - Gene Expression MH - Gene Expression Profiling MH - Humans MH - In Situ Hybridization, Fluorescence MH - Multiple Myeloma/*genetics MH - Oligonucleotide Array Sequence Analysis MH - Oncogene Proteins, Fusion/*genetics MH - *Protein-Tyrosine Kinases MH - RNA, Messenger/analysis MH - Receptor, Fibroblast Growth Factor, Type 3 MH - Receptors, Fibroblast Growth Factor/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - *Translocation, Genetic EDAT- 2002/11/16 04:00 MHDA- 2003/04/08 05:00 CRDT- 2002/11/16 04:00 PHST- 2002/11/16 04:00 [pubmed] PHST- 2003/04/08 05:00 [medline] PHST- 2002/11/16 04:00 [entrez] AID - S0006-4971(20)57359-X [pii] AID - 10.1182/blood-2002-09-2801 [doi] PST - ppublish SO - Blood. 2003 Mar 15;101(6):2374-6. doi: 10.1182/blood-2002-09-2801. Epub 2002 Nov 14.