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.
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.
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 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).
Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically.
Cyclin D1 gene amplification was found in 20% of myeloma patients and was associated with higher percentage of plasma cell infiltration of the bone marrow and increased liability for multiple osteolytic lesions.
This gene was found to be rearranged and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32)-positive multiple myeloma (MM) cell lines.
To define further the prevalence of this abnormality in multiple myeloma, we studied a series of 17 patients with this disease with concomitant chromosome analysis and Southern blotting, using a probe specific for the major translocation cluster of the BCL-1 oncogene which is located at chromosome 11q13.
Translocation t(11;14)(q13;q32)CCND1-IGH is typically associated with mantle cell lymphoma or a subset of plasma cell myeloma and is exceedingly rare in myeloid neoplasm.
We used two independent MM cell lines (RPMI 8226 and LP1) to generate several clones stably expressing either the green fluorescent protein (GFP) or a GFP-cyclin D1 fusion protein, and we analyzed the properties acquired following cyclin D1 expression.
We therefore quantified levels of total and Delta3'UTR cyclin D1 mRNA by real-time RT-PCR in cytogenetically characterized cyclin D1+MM primary cases, and cyclin D1+cell lines.
We established several clones that constitutively express cyclin D1 from the parental RPMI8226 MM cell line and analyzed the impact of cyclin D1 expression on cell behavior.
There is a promiscuous array of nonrandom chromosomal partners (and oncogenes), with the 3 most frequent partners (11q13 [cyclin D1]; 4p16 [FGFR3 and MMSET]; 16q23 [c-maf]) involved in nearly half of MM tumors.