Molecular Pathology Laboratory Network

F FGFR3

t(4;14)(p16;q32)

Myeloma, monoclonal gammopathy (MGUS)

Fluorescence in situ Hybridization (FISH)

88367 x2 - Morphometric analysis, in situ hybridization, automated
88368 x2 - Morphometric analysis, in situ hybridization, manual

3 days

• 2.0 mL (min. 1.0 mL) peripheral blood in sodium heparin preferred, EDTA accepted
• 1.0 mL (min. 0.5 mL) bone marrow in sodium heparin preferred, EDTA accepted
• 5 mm^3 fresh tissue in MPLN RPMI media
• 3.0 mL (min. 2.0 mL) FNA in MPLN RPMI media
• 10% neutral buffered formalin fixed paraffin embedded tissue

• Peripheral blood and bone marrow stable at 18-25°C for 72 hours
• Fresh tissue or FNA stable at 2-8°C for 72 hours

• Whole blood and bone marrow, ship ambient
• Fresh tissue, FNA or paraffin embedded tissue ship in a Styrofoam container with an ice pack (Do not allow ice pack to directly contact sample)

Clotted specimen; Specimen exposed to extreme temperature; Anticoagulant toxic to cells; Insufficient number of cells; Improper fixative

In a normal cell, a two orange and two green signal pattern is observed reflecting the two intact copies of the FGFR3 and IGH regions. In an abnormal cell, one orange (FGFR3), one green (IGH), and two fusion signal pattern (der (4) and der (14)) is observed.

The t(4;14) translocation is found in approximately 10% of myeloma patients and results in the deregulation of at least two genes, MMSET and fibroblast growth factor receptor 3 (FGFR3), with the formation of a fusion product between MMSET and the immunoglobulin heavy chain (IGH) locus and overexpression of FGFR3. In monoclonal gammopathy of undetermined significance (MGUS), a similar proportion of t(4;14) positive cases are found, but none of these express FGFR3. FISH can detect this translocation in either interphase or metaphase cells.