XL IGH/MAFB DF consists of a green-labeled probe hybridizing to the IGH gene region at 14q32.3 and an orange-labeled probe hybridizing to the MAFB gene region 20q12.

Probe maps are created in accordance with the intended purpose of the product. Solid colored bars do not necessarily indicate that the probe fully covers the indicated genomic region. Therefore, caution is advised when interpreting results generated through off-label use. Probe map details based on UCSC Genome Browser GRCh37/hg19. Map components not to scale. Further information is available on request.

The most frequent primary abnormalities in multiple myeloma (MM) are trisomies of odd-numbered chromosomes or translocations involving the immunoglobulin heavy chain (IGH) gene locus. The most common MM-associated IGH translocations are t(11;14), t(4;14), t(6;14), t(14;16) and t(14;20) in the order of their occurrence. As a consequence, translocation partner genes of IGH are dysregulated, as they are juxtaposed to transcriptional enhancers in the IGH locus. Prognosis and risk classification are strongly associated with the detection and interpretation of cytogenetic primary abnormalities. According to the International Myeloma Working Group (IMWG), risk classification of MM by FISH based analysis of IgH locus involving translocations represents one column of the entire diagnostics. Secondary effects are also influencing the outcome. Even if associated with poor prognosis in MM, MGUS/SMM cases characterized by the presence of t(14;20) can be stable for years before progression occurs, whereas MGUS/SMM cases with t(4;14) and t(14;16) show a significantly faster progression rate. The recurrent translocation t(14;20) (q32;q12) results in ectopic expression of the basic leucine zipper transcription factor MAFB (Vmaf musculoaponeurotic fibrosarcoma oncogene homolog B) which plays an important role in lineage-specific hematopoiesis. Furthermore, t(14;20) is associated with poor prognosis by promoting high cyclin D2 activity, thereby dysregulating normally balanced cell cycle.

Clinical Applications

• Multiple Myeloma and Plasma Cell Neoplasms (MM)

XL IGH/MAFB DF hybridized to bone marrow cells, one aberrant cell is shown. A translocation t(14;20) has occurred generating a signal pattern of two colocalization/fusion signals, one green and one orange signal.

• Boersma-Vreugdenhil et al (2004) Brit J Haem 126:355-363
• Ross et al (2010) Haematologica 95:1221-1225
• Rajan and Rajkumar (2015) Blood Cancer J 5:e365

• Utility and performance of bacterial artificial chromosomes-on-beads assays in chromosome analysis of clinical prenatal samples, products of conception and blood samples.
• A child with multiple congenital anomalies due to partial trisomy 7q22.1 → qter resulting from a maternally inherited balanced translocation: a case report and review of literature.
• Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.
• Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study.
• Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4-ALK fusion.
• Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation.
• Fluorescence in situ hybridisation assays designed for del(7q) detection uncover more complex rearrangements in myeloid leukaemia cell lines
• A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasiaresulting in a fusion of IGL and CCND1: case report.
• Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions.