IGH/BCL2 Translocation Probe Dual Fusion

This is cytogenetically indistinguishable from the t(14;18) translocation observed in follicular lymphoma and is the second most common rearrangement of IGH in CLL. The translocation is thought to be brought about by an error in the joining function of the IGH gene, mediated by the recent observation that both IGH and BCL2 are arranged next to each other in the normal B lymphocyte. The translocation breakpoint at the end of the Joining (J) segment and the subsequent fusion of the BCL2 gene to this region results in the BCL2 gene coming under the regulatory control of those processes normally involved in maintenance of IGH gene activity. The BCL2 gene itself has been shown to be involved in the regulation of apoptosis and is unusual in that the protein is an integral part of the mitochondrial inner membrane.

The green probe covers the Constant and Variable segments of the IGH gene, whilst a probe contig. measuring 605 kb, covers the BCL2 and FVT1 genes on chromosome 18 and is labelled in red. In the normal cell, these probes will appear as discrete red and green spots, one for each homologue (resulting in a 2G 2R conformation). In a t(14:18) patient, the Constant region probe of the IGH swaps with the proximal portion of the BCL2 contig and vice versa resulting in two (yellow) fusion signals in addition to the red and green signals of the normal chromosomes 18 and 14 respectively (1R 1G 2Y).