IGH/CCND3 Translocation, Dual Fusion LPH040 - Detail

Approximately 40-60% of multiple myeloma cases are associated with translocations involving the IgH locus at chromosome 14q32 and one of several partners including CCND1, MMSET, CCND3, cMAF and MAFB. Cases lacking an IgH translocation are associated with hyperdiploid phenotype¹. The CCND3/IGH translocation t(6;14)(p12-p21;q32) has been reported in 3-4% of multiple myeloma tumours². However it is also characteristic of a variety of other B-cell malignancies including plasma cell leukaemia, diffuse large B-cell non-Hodgkin lymphoma (DLBCL) and splenic marginal zone lymphomas (SMZLs) ³. Cyclin D3 has been identified as a putative oncogene that is dysregulated as the consequence of the translocation². The translocation appears to be mediated by an error in IgH switch recombination because it has been shown that in KMM-1 cell lines, the translocation disrupts a switch sequence in this region and results in juxtaposition of CCND3 with the IGH promoter thus elevating the levels of CCND3 expression². It is thought that this mechanism is similar in all cases of IgH translocation. Most breakpoints appear to be clustered in a region that is fewer than 200kb centromeric to CCND3² and it is this region that is flanked by the Cytocell probe.

Reference:/Bibliographie/Literatur/Bibliografia

1. Fonseca et al Cancer Research 64, 1546-1558, February 15, 2004
2. Shaughnessy et al Blood 2001; 98(1): 217-223
3. Soniki et al Blood 2001; 98(9): 2837-2844