Our results confirm previous findings that the 11q13 breakpoints in MM are scattered throughout the 11q13 region encompassing the cyclin D1 gene, thus suggesting the absence of 11q13 breakpoint clusters in MM.
Our data indicate that deregulation of MYEOV is not favored in MM and further strengthens the role of cyclin D1 overexpression in lymphoid malignancies with a t(11;14)(q13;q32) translocation.
Among recurrent IGH translocations in MM, the frequency of t(4;14) (IGH and FGFR3) or t(11;14) (IGH and CCND1) is greater than the frequency of t(14;16) (IGH and MAF).
In this study, the prognostic significance of morphology, CyclinD1 expression, proliferation index (Mib1) and presence of the translocations FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with PM.
In contrast, double-color fluorescence in situ hybridization analysis showed that BM-derived CD138-positive myeloma cells possessed the gene translocation between the immunoglobulin heavy chain gene and the cyclin D1 gene, which was not involved in non-myeloma hematopoietic cells.
Mutation of Lys650-->Glu in the activation loop of the FGFR3 kinase domain causes the lethal human skeletal disorder thanatophoric dysplasia type II (TDII) and is also found in patients with multiple myeloma, bladder and cervical carcinomas.
Among recurrent IGH translocations in MM, the frequency of t(4;14) (IGH and FGFR3) or t(11;14) (IGH and CCND1) is greater than the frequency of t(14;16) (IGH and MAF).
The t(11;14)(q13;q32) results in up-regulation of cyclin D1 and is the most common translocation detected in multiple myeloma, where it is also associated with a lymphoplasmacytic morphology.
The karyotypically silent t(4;14)(p16.3;q32) translocation can be found in approximately 15-20% of multiple myeloma (MM) patients and results in the ectopic expression of fibroblast growth factor receptor 3 (FGFR3) from der4.
This study demonstrated that CCND1 and FGFR3 genes are involved together in about 50% of MM and primary PCL patients with illegitimate IGH rearrangements.
Dysregulation of cyclin D1 by a t(11;14)(q13;q32) translocation occurs in most cases of mantle-cell lymphoma and in approximately 30% of multiple myeloma (MM) tumors in which a 14q32 translocation can be detected.
The ectopically expressed fibroblast growth factor receptor 3 (FGFR3) and its constitutively active mutations have been detected in patients with multiple myeloma (MM).
Nearly 40% of MM tumors have immunoglobulin H (IgH) translocations involving four recurrent chromosomal loci (oncogenes): 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (MMSET and FGFR3), and 16q23 (c-maf).
The t(11;14)/CCND1-IGH, t(4;14)/NSD2(MMSET)-IGH, and t(14;16)/IGH-MAF gene rearrangements detected by fluorescence in situ hybridization (FISH) are used for risk stratification in patients with multiple myeloma (MM).