IGH/MAF Translocation, Dual Fusion LPH029 - Detail

The translocation t(14;16) (q32.3;q22) involving c-MAF and IGH is present in 25% of myeloma cell lines¹, in 2-6% of primary Multiple Myeloma samples^2,3 and results in high levels of c-MAF expression. Patients harbouring t(14;16) appear to have a worse outcome^3,4. The majority of the breakpoints are dispersed over an approximate 500kb region centromeric to the c-MAF proto-oncogene at 16q23. Other breakpoints however have been seen telomeric to c-MAF1. Translocation with the centromeric breakpoints places c-MAF under the control of the strong 3' IGH enhancer. Recent gene expression profiling of myeloma cell lines revealed that c-MAF transactivated cyclin D2 (a promoter of cell cycle progression), thus enhancing proliferation of myeloma cells⁴. The putative tumour suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D) at chromosome 16q23.3-24.1 and this region is a frequent target for loss of heterozygosity and chromosomal rearrangements in ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias⁵. WWOX is contained within the breakpoint region of the c-MAF-IGH translocation.

Reference:/Bibliographie/Literatur/Bibliografia

1. Chesi M et al (1998) Blood 12; 4457-4463
2. Avet-Loiseau H et al (2002) Blood 99; 2185-2191
3. Fonseca R et al (2003) Blood 101; 4569-4575
4. Chang H et al (2007) Leukemia 21; 1572-1574
5. Nunez MI et al (2005) BMC Cancer 5; 64