Test Directory

• BCL2 ,18q21.31-q21.32 Rearrangement
• MYC, 8q24.21 Rearrangement
• BCL6 ,3q27.3-q28 Rearrangement
• MYC::IGH, t(8;14)
• IGH ,14q32.3 Rearrangement
• IGH::BCL2, t(14;18)

This panel differentiates double-hit or triple-hit lymphomas (which have MYC rearrangements together with BCL2 and/or BCL6 rearrangements) from Burkitt lymphoma or diffuse large B-cell lymphoma. Double-hit and triple-hit lymphomas are difficult to classify morphologically without the aid of cytogenetics/FISH or IHC, and are associated with an aggressive course. Testing is indicated when B-cell lymphoma patients experience transformation, relapse, or refractory disease.

Diffuse large B-cell lymphoma / high-grade B-cell lymphoma with MYC and BCL2 rearrangements (DLBCL/HGBCL-MYC/BCL2) is an aggressive mature B-cell lymphoma with structural chromosomal aberrations with breakpoints at both MYC and BCL2 loci. DLBCL/HGBCL-MYC/BCL2, by definition, harbors two oncogenic rearrangements: one targeting MYC and one targeting BCL2. Their often-aggressive behavior is postulated to be the result of aberrant expression of BCL2, leading to increased apoptotic resistance, and MYC activation, driving proliferation.

MYC rearranges with an immunoglobulin partner in approximately 60% of MYC-rearranged DLBCL/HGBCL of which 75% are MYC/IGH fusion. BCL2 (18q21) is primarily translocated to IGH (14q32). MYC (8q24) translocation is more diverse and is to IG loci in 55–58% of cases – predominantly IGH, alternatively IGL via t(8;22)(q24;q11), or, more rarely, IGK via t(2;8)(p11;q24). A reflex panel to rule out these partners is offered for IGK and IGL.

BCL6::MYC reciprocal translocations as previously designated as having triple-hit status (now considered pseudo–triple-hit) as well as some cases of DLBCL/HGBCL with MYC and BCL6 rearrangements (pseudo–MYC/BCL6 double-hit). However, the relative frequency of reciprocal BCL6::MYC translocations and the impact on MYC and BCL6 locus regulation remain undetermined. 

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

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 specimen 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

BCL2, 18q21.33-q22.1 Breakapart Probe-Rearrangement

In a normal cell, the expected signal pattern is two fused signals. In an abnormal cell with a rearrangement, the expected signlal pattern is one red signal, one green signal, and one fused signal.

MYC, 8q24.21 Breakapart Probe-Rearrangement

In a normal cell, the expected signal pattern is two fused signals. In an abnormal cell with a rearrangement, the expected signal pattern is one red signal, one green signal, and one fused signal.

BCL6, 3q27 Breakapart Probe-Rearrangement

In a normal cell, the expected signal pattern is two fused signals. In an abnormal cell with a rearrangement, the expected signal pattern is one red signal, one green signal, and one fused signal.

MYC::IGH, t(8;14) Translocation Probe

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

IGH, 14q32.3 Breakapart Probe-Rearrangement

In a normal cell, the expected signal pattern is two fused signals. In an abnormal cell with a rearrangement, the expected signal pattern is one red signal, one green signal, and one fused signal.

IGH::BCL2, t(14;18) Translocation Probe

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

• FISH NHL B-cell High Grade Lymphoma Panel, Heme

• Associations:
• Burkitt's Lymphoma (BL)
• Diffuse Large B-cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)