Comparison of IGH Profile Signals Using t(4;14) and IGH Break-Apart Probes by FISH in Multiple Myeloma.

We compared immunoglobulin heavy chain gene (IGH) signal patterns in multiple myeloma (MM) using the FGFR3-IGH and the IGH break-apart probes to facilitate their understanding and analysis. Forty-nine patients with MM were studied. FISH was performed on samples sorted with an FGFR3-IGH dual-color, dual-fusion translocation probe and an IGH dual-color break-apart rearrangement probe. The IGH deletions were found in 7 MM analyzed with the FGFR3-IGH probe and all confirmed by the IGH break-apart probe. The additional IGH signals were associated with different patterns using the IGH break-apart probe: a normal pattern in 9 cases, trisomy 14 in 3 cases, and splits of IGH in 7 cases. Fusion patterns with the FGFR3-IGH probe were observed in 13 cases. Atypical patterns were identified in 6 cases with multiple presentations of IGH: a deletion of the IGH variable segment in der(4) or in chromosome 14, loss of the IGH locus in chromosome 14, and additional copies of FGFR3-IGH fusion probes. We identified a majority of atypical IGH patterns with the t(4;14) probe, without false-negative results when FGFR3-IGH signal fusions were found. However, the extrapolation of FGFR3-IGH probe signals requires the IGH break-apart probe to obtain unequivocal interpretations.