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Interphase detection of t(4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell
N Nakazawa1, K Nishida, A Tamura
1Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Abstract:
The immunoglobulin (Ig) genes are frequently involved in chromosomal rearrangements with a wide variety of partner loci in multiple myeloma (MM). However, several partner chromosomes have not been detected by conventional cytogenetic 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 the 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 MM-two with plasmacytoma (PCM) and three with plasma cell leukemia (PCL). All patients were studied by DC-FISH; 40 were studied by G-banding and 36 were studied by RT-PCR. The FISH probes consisted of a cosmid pC385.12 containing the FGFR3 gene, a YAC Y6 containing VH, and a phage Iggamma1-10 containing the gamma1 constant region (Cgamma). We identified eight patients with either FGFR3/Cgamma fusion or FGFR3 overexpression: six patients with both FGFR3/Cgamma fusion and FGFR3 overexpression, one patient with FGFR3/Cgamma, and one with FGFR3 overexpression. FGFR3/Cgamma fusion was demonstrated at a frequency of 19% to 38% on interphase nuclei in seven of the 45 patients. Lytic bone lesions were found to be associated with FGFR3 overexpression. Interphase FISH with FGFR3 and Cgamma probes combined with RT-PCR proved to be an effective tool for detection of this fully cryptic translocation, thus facilitating the characterization of clinical features of MM patients with t(4;14).
Insights
Chromosomal rearrangements involving immunoglobulin genes are common in multiple myeloma (MM). This study identified the t(4;14) translocation in MM patients using advanced FISH and RT-PCR techniques, linking FGFR3 overexpression to lytic bone lesions.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Immunoglobulin (Ig) genes in multiple myeloma (MM) frequently undergo chromosomal rearrangements.
- Several MM-associated partner chromosomes, including 4p16.3 (FGFR3), are difficult to detect with conventional cytogenetics.
Purpose of the Study:
- To determine the incidence of the t(4;14)(p16.3;q32.3) translocation in primary MM tumors.
- To evaluate the correlation between this translocation and specific MM disease manifestations.
Main Methods:
- G-banding, double-color fluorescence in situ hybridization (DC-FISH), and reverse-transcriptase polymerase chain reaction (RT-PCR) were used.
- FISH utilized probes for FGFR3, VH, and the gamma1 constant region (Cgamma).
- The study included 40 MM patients, 2 with plasmacytoma (PCM), and 3 with plasma cell leukemia (PCL).
Main Results:
- The t(4;14) translocation, indicated by FGFR3/Cgamma fusion or FGFR3 overexpression, was detected in 19% to 38% of patients.
- Eight patients showed either FGFR3/Cgamma fusion or FGFR3 overexpression.
- FGFR3 overexpression was significantly associated with lytic bone lesions.
Conclusions:
- Interphase FISH and RT-PCR are effective for detecting the cryptic t(4;14) translocation in MM.
- This diagnostic approach aids in characterizing clinical features of MM patients with t(4;14).