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[Cancer Research 60, 4058-4061, August 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

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

Ursula Malgeri, Luca Baldini, Vittorio Perfetti, Sonia Fabris, Maurizio Colli Vignarelli, Gualtiero Colombo, Valentina Lotti, Silvana Compasso, Silvia Bogni, Luigia Lombardi, Anna Teresa Maiolo and Antonino Neri2

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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