Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF

Abstract

Many B-cell tumors have chromosomal translocations that result from failures of the immunoglobulin (Ig) gene during V(D)J recombination, somatic hypermutation (SHM), and class switch recombination (CSR). Nearly half of all multiple myeloma (MM) patients have 14q32/IGH translocations in CSR, including the five common translocations of 11q13/CCND1, 6p21/CCND3, 4p16/FGFR3, 16q23/MAF, and 20q11/MAFB. Although 14q32/IGH translocations are closely related to the biological features of MM, the most consistent and powerful prognostic factor has been reported to be the loss of all (monosomy 13/-13) or part of chromosome 13 (del(13)(q14)/13q-). Our fluorescence in situ hybridization (FISH) analysis method was designed to detect -13/13q- and 14q32/IGH rearrangements in 23 MM patients. FISH disclosed 14q32/IGH translocations in 10 of the 23 (43.5%) patients. The common translocation partners of 14q32/IGH were 11q13/CCND1 (five patients) and 16q23/MAF (four patients), followed in third place by 4p16/FGFR3 (one patient). Nine of the ten patients carrying 14q32/IGH translocations had -13/13q-. Abnormalities of chromosome 13 included -13 in seven (70%) and del(13)(q14) in two (20%). Our results suggest a significant correlation between the presence of 14q32/IGH translocations and chromosome 13 abnormalities (P = 0.0276) in MM patients.

Molecular Cytogenetic Aberrations in Tunisian Patients with Multiple Myeloma Identified by cIg-FISH in Fixed Bone Marrow Cells

“…In our study, the most frequent 14q32 translocation was t(11; 14)(q13;q32), found in 25.7% of the 70 patients analyzed. This was similar to what recently has been reported by Takimoto et al [2008], i.e. 21.7% among Japanese patients.…”

“…12.5% found by Chen et al [2007] in China. The t(4; 14) and t(14; 16) translocations were found in our series with frequencies of 11.4% and 2.4%, respectively, compared to the 4.3% and 17.2% recently described by Takimoto et al [2008]. Our findings on these latter translocations are, however, compatible to those described by Chen et al [2007] and Hoyer et al [2000].…”

“…In accordance with previous reports, the most frequent chromosomal abnormality that we observed was a 14q32/ IGH rearrangement, seen in 32 (45.7%) of our patients. This prevalence is lower than that reported by most other investigators using I-FISH in conjunction with purified PC [Chen et al, 2007;Yuregir et al, 2009] Takimoto et al [2008] in Japan, who found 14q32 translocations in 43.5% of the cases. These translocations are considered as early primary events that are mediated by errors in IGH switch recombination or somatic hypermutation during the maturation of B cells in germinal centers [Mohamed et al, 2007].…”

The role of circulating miRNAs in multiple myeloma

“…Detailed genomic analysis has revealed that MM was characterized by complex cytogenetic abnormalities, such as chromosomal translocations involving mutations of t(4;14), t (6;14) and t(14;16); deletion of 13q14 and 17p13; rearrangement of immunoglobulin heavy-chain genes (IGH); and amplification of 1q21 [50][51][52][53]. The tumor suppressor p53 which is located in 17p13.1 is rarely inactivated by [42] mutations or deletions, the ectopic expression of p53 can downregulate miR-192, miR-194, and miR-215 in a subset of newly diagnosed MM patients.…”

HDAC1 promotes the migration of human myeloma cells via regulation of the lncRNA/Slug axis

“…Genetic and epigenetic abnormalities, such as chromosomal translocations and histone acetylation, are common features of MM (9)(10)(11)(12). Histone deacetylases (HdAcs) can remove acetyl groups from N-acetyllysines on histones to regulate the progression of various cancer types, including MM (13).…”