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Detection of t(4;14)(p16.3;q32) Chromosomal Translocation in Multiple Myeloma by Reverse Transcription-Polymerase Chain Reaction Analysis of IGH-MMSET Fusion Transcripts¹

Hematology Service [U. M., L. B., S. F., V. L., S. C., S. B., L. L., A. T. M., A. N.] and 3rd Division of Internal Medicine [G. C.], Università degli Studi di Milano, Ospedale Maggiore IRCCS, 20122 Milan, and Department of Internal Medicine [V. P.] and Biotechnology Research Laboratories [M. C. V.], Policlinico San Matteo IRCCS, 27100 Pavia, Italy

We and others have recently identified a novel recurring t(4;14)(p16.3;q32) translocation in multiple myeloma (MM) that leads to an apparent deregulation of the FGFR3 and WHSC1/MMSET genes. Because the presence of IGH-MMSET hybrid transcripts has been found in MM cell lines with t(4;14), they may represent a specific tumor-associated marker in MM. In this study, we developed a reverse transcription-PCR (RT-PCR) assay for detecting chimeric transcripts from all of the 4p16.3 breakpoints identified thus far, and we used it to investigate a representative panel of 53 MM patients and 16 patients with monoclonal gammopathy of uncertain significance; in addition, t(4;14) was investigated in all of the MM patients by means of two-color fluorescence in situ hybridization. IGH-MMSET transcripts were found in 11 of the 53 (20%) MM cases and 1 of 16 (6%) cases of monoclonal gammopathy of uncertain significance. There was complete concordance between the RT-PCR and fluorescence in situ hybridization analyses of the MM cases. The results of this study indicate that RT-PCR is a sensitive and reliable method of detecting t(4;14) and suggest that it may be useful for monitoring the disease in a significant proportion of patients.

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