Detection of the t(4;14)(p!6.3;q32) chromosomal translocation in multiple myeloma by rt-pcr analysis of 1gh-mmset fusion transcripts

The t(4;14)(pl6.3;q32) chromosomal translocation is a recurrent genetic lesion in multiple myeloma (MM) leading to the apparent deregulation of FGFR3 and WHSC1/ MMSET genes. MM-derived cell lines carrying the t(4;14) were found to generate 1GH-MMSET hybrid transcripts as a result of the translocation. These transcripts may represent a specific tumor-associated marker for the detection of t(4;14) in MM. We developed an RT-PCR assay for detecting hybrid transcripts generated from all of the 4pl6.3 breakpoint types identified so far and investigated a panel of 53 patients affected by MM and 16 patients with a monoclonal gammopathy of uncertain significance (MGUS). Doublecolor FISH was performed in all of the MM patients in order to identify the t(4;14). IGHMMSET transcripts were found in 11 (20%) of the 53 cases of MM analyzed and in only one (6%) of the 16 MGUS patients. A complete concordance between RT-PCR and FISH analyses was observed in MM patients. Our data indicate that RT-PCR is a sensitive and realiable method of detecting the t(4;14) translocation in MM and suggest that it may be useful for monitoring the disease in a significant proportion of patients.