Test Directory

• FGFR3, 4p16.3
• IGH, 14q32.3

The t(4;14) is found in plasma cell leukemia, multiple myeloma, plasmacytoma and monoclonal gammopathy of unknown significance (MGUS). It represents the second more frequent immunoglobulin heavy chain (IGH) associated rearrangement, after t(11;14). The t(4;14) is detected by interphase FISH or RT-PCR in 25% of multiple myeloma (MM) cell lines, 15-20% primary MM and 0-10% MGUS lines. This translocation is karyotypically undetected. The t(4;14) generates two fusions genes. In the first fusion gene, the fibroblast growth factor receptor 3 (FGFR3) is brought under the influence of the Ig gene enhancer Ea on der(14). In the second fusion gene, the multiple myeloma SET domain (MMSET) is under the influence of the enhancer Eµ on der(4). Both FGFR3 and MMSET genes are deregulated by translocation. An IGH-MMSET fusion transcript (detectable by RT-PCR) is generated. There is no IGH::FGFR3 fusion protein, but there is promoter exchange between both partner genes. However, somatic mutations similar to what has been found in thanatophoric dwarfism have been identified in some cases, which may also contribute to the abnormal FGFR3 activation. The presence of a t(4;14) has an unfavorable prognosis, even in patients treated with high dose chemotherapy. Additional abnormalities are hypodiploid karyotype and -13 / 13q- in major part of cases.

Specimen Types: Leukemic Blood or Bone Marrow

Preferred Collection Container: Green Top (Sodium Heparin)

Alternate Collection Container: Lavendar Top (EDTA)

Desired Specimen Volume: 3 - 5 mL

Minimum Acceptable Volume: 1 mL

• Lithium heparin is not acceptable.
• Specimens must be collected in a sterile collection container. Do not open tube.

Each specimen must be accompanied by a requisition form, script, electronic order or physician note. Each order must indicate the reason for testing (diagnosis).

• Transport to the laboratory at room temperature.
• Store specimen as whole blood, in original tube, at room temperature and deliver to lab within 24 hours.
• If specimen cannot be delivered within 24 hours, store in refrigerator. Do not freeze specimen.
• Specimens collected on the weekends must be refrigerated upon arrival at HNL Lab Medicine.

• Specimen frozen
• Specimen arriving without any form of patient identification (unlabeled)
• Specimen with attached needles
• Specimen arriving with broken or leaking collection tube
• Unfixed specimen treated with fixative

In a normal cell, the expected signal pattern is two orange signals and two green signals. In an abnormal cell containing a typical translocation, the expected signal pattern is one orange signal, one green signal, and two fused signals.

• FISH Translocation IGH/FGFR3
• t(4;14)
• IGH::FGFR3
• Fibroblast Growth Factor Receptor 3