• Test Code:
    4070
  • Department:
  • Test Synonyms:
    Immunoglobulin (IgH) Gene RearrangementImmunoglobulin (IgH) ClonalityImmunoglobulin light chain clonalityKappa gene rearrangementKappa gene clonalityGene rearrangements for B-cell lymphoma;B cell gene rearrangement for clonality
  • CPT Code(s):
    8126181264
Background:

B-cell lymphomas account for greater than 90% of non-Hodgkin lymphomas and may pose a diagnostic challenge on the basis of histopathology alone.  During normal B-cell maturation, the immunoglobulin heavy chain gene is rearranged such that each mature B-cell and plasma cell has a unique rearranged heavy chain gene profile.  This process is vital to proliferation of B-cells in normal immune function, but can be exploited to aid in the distinction between reactive (benign) versus neoplastic processes of B-cell proliferation.  A reactive, benign B-cell proliferation is characterized by polyclonal expansion of B-cells whereas a malignant process is often characterized by a clonal expansion of a predominant B-cell population.  In conjunction with the histopathology study of lymph nodes, bone marrow and other tissue types, the detection of a clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) is intended as an aid in the diagnosis of malignant B-cell lymphoma.

Clinical Utility: 
PCR-based detection of rearranged immunoglobulin heavy chain genes can be used as an aid to establish a diagnosis of a B-cell lymphoma, plasma cell malignancy, monitor treatment response, and/or measure minimal residual disease (MRD).

Methodology:

Genomic DNA is extracted from blood, lymph node, bone marrow, or other tissue types and the rearranged immunoglobulin heavy chain genes are amplified by PCR using a multiplex primer method based on the BIOMED-2 strategy.  Precise fragment sizing of the amplicons is accomplished using capillary gel electrophoresis.  The presence or absence of a monoclonal population is determined based on the overall analysis of the gel electrophoretic pattern.

Clinical Sensitivity:  > 95% for the detection of clonality in most tissue types. 

Clinical Specificity: As cross-lineage immunoglobulin heavy chain gene rearrangements have been reported in certain T-cell malignancies, interpretation of this test requires clinical, morphologic, and immunophenotypic correlation.

Specimen Requirements:

  • 5-10 mL of blood or bone marrow — yellow (ACD) or purple (EDTA) tube.Store and ship refrigerated.
  • If sending DNA, please send 200ng at a minimum of 10ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
  • Formalin-fixed paraffin-embedded (FFPE) tissue blocks or 10 slides (5 microns).Store and ship at room temperature
  • Fresh Tissue:
    • Stabilize in Allprotect Tissue Reagent (Qiagen) and ship at room temperature – OR
    • Suspend in sterile culture media (RPMI or DMEM) or non-bacteriostatic normal saline in a sterile container and shipped at room temperature – OR
    • Snap Frozen and shipped on dry ice
  • Pathology report MUST accompany sample for interpretation of results.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information.

Test Performed (Days):

Twice per week

Turn Around Time:

5-10 days

Shipment Sensitivity Requirements:

  • Keep specimen cold during transit, but do not ship on dry ice. 
  • Please use the cold pack provided in the KDL shipping kit. 
  • Ship the specimen overnight express, using the FE priority overnight label provided. 

References:

  1. Van Dongen JJ, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.  Leukemia 2003; 17(12):2257-2317.
  2. Langerak AW, Molina TJ, Lavender FL, et al.  Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. Report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2007; 21:222-229.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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