Interphase detection of t(4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell malignancies

The immunoglobulin (Ig) genes are frequently involved in chromosomal rearra ngements with a wide variety of partner loci in multiple myeloma (MM). Howe ver, several partner chromosomes have not been detected by conventional cyt ogenetic methods; for example, 4p16.3 (FGFR3), 6p25.3 (IRF4), and 16q23 (c- maf). To clarify the incidence of t(4;14)(p16.3/q32.3) in primary tumors of MM and to evaluate possible correlations with specific manifestations of t he disease, G-banding, double-color fluorescence in situ hybridization (DC- FISH), and/or reverse-transcriptase polymerase chain reaction (RT-PCR) were performed on 40 patients with IMM-two with plasmacytoma (PCM) and three wi th plasma cell leukemia (PCL). All patients were studied by DC-FISH; 40 wer e studied by G-banding and 36 were studied by RT-PCR. The FISH probes consi sted of a cosmid pC385.12 containing the FGFR3 gene, a YAC Y6 containing VH , and a phage Ig gamma 1-10 containing the gamma 1 constant region (C gamma ). We identified eight patients with either FGFR3/C gamma fusion or FGFR3 o verexpression: six patients with both FGFR3/C gamma fusion and FGFR3 overex pression, one patient with FGFR3/C gamma, and one with FGFR3 overexpression . FGFR3/C gamma fusion was demonstrated at a frequency of 19% to 38% on int erphase nuclei in seven of the 45 patients. Lytic bone lesions were found t o be associated with FGFR3 overexpression. Interphase FISH with FGFR3 and C gamma probes combined with RT-PCR proved to be an effective tool for detec tion of this fully cryptic translocation, thus facilitating the characteriz ation of clinical features of MM patients with t(4;14). (C) Elsevier Scienc e Inc., 2000. All rights reserved.