XL t(4;14) FGFR3/IGH DF consists of an orange-labeled probe hybridizing to the FGFR3 gene region at 4p16.3 and a green-labeled probe hybridizing to the IGH gene region at 14q32.3.

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 immunglobulin 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. The consequence of these rearrangements is the dysregulation of genes juxtaposed to transcriptional enhancers in the IGH locus. Prognosis and risk stratification strongly depend on the detection and interpretation of cytogenetic primary abnormalities. t(14;16) and t(14;20) are considered as high risk, t(4;14) as intermediate risk and t(6;14) and t(11;14) as standard risk cytogenetic aberrations in patients with MM based on FISH testing. Secondary aberrations are also influencing the outcome.
The recurrent translocation t(4;14)(p16;q32) is juxtaposing FGFR3 with the 3′ alpha IgH enhancer on der(14), whereas expression of NSD2 is controlled by the Eμ enhancer on der(4). FGFR3 overexpression is detectable in about 70% of t(4;14) positive MM patients, suggesting that FGFR3 dysregulation is not the crucial oncogenic event. The poor outcome of patients lacking FGFR3 expression due to the loss of der(14) is supporting this conclusion. Transcripts from the NSD2 locus on the other hand are found to be overexpressed in all t(4;14) positive MM cases, suggesting that this gene region plays a major role in the manifestation of MM.

Clinical Applications

• Multiple Myeloma and Plasma Cell Neoplasms (MM)

XL t(4;14) IGH/FGFR3 DF hybridized to lymphocytes. Two normal interphases are shown.

• Chesi et al (1998) Blood 92:3025-3034
• Keats et al (2003) Blood 15:4060-4069
• 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.
• Fluorescence in situ hybridisation assays designed for del(7q) detection uncover more complex rearrangements in myeloid leukaemia cell lines
• Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation.
• 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.