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CAT #: 13080020

BCL1/JH Translocation Assay MegaKit - Gel Detection

Product Use

BCL1/JH t(11;14) Translocation Assays are useful for the study of:

  • Identifying BCL1/JH gene rearrangements highly suggestive of mantle cell lymphoma
  • Lineage determination of leukemias and lymphomas
  • Monitoring and evaluation of disease recurrence
  • Detection and assessment of residual disease
  • Evaluation of new research and methods in malignancy studies

Product Details

  • Summary of Explanation of the Test

    SUMMARY:

    Invivoscribe’s Gene Rearrangement and Translocation Assays represent a new approach to PCR-based clonality testing. These standardized assays were carefully optimized testing positive and negative control samples using multiplex master mixes.

    BACKGROUND:

    The t(11;14)(q13;q32) is mainly found in mantle cell lymphoma, but has also seen in B-prolymphocytic leukaemia (10-20%), plasma cell leukaemia, splenic lymphoma with villous lymphocytes, chronic lymphocytic leukaemia (2-5%), and in multiple myeloma (20-25%). (Huret JL. t(11;14)(q13;q32). Atlas Genet. Cytogenet. Oncol. Haematol. May 1998). Fluorescence-in-situ-hybridization (FISH) with probes flanking the BCL1 translocation breakpoint cluster region at chromosome 11 band q13, revealed that all mantle cell lymphomas (as defined by the REAL-classification) carry the t(11;14)(q13;q32) (Coignet 1996; Vaandrager 1996). The breakpoints are scattered over a region of 350-kb and ~41% of these breakpoints subcluster in a locus of only 1-kb referred to as the BCL1-major-translocation-cluster, the BCL1-MTC, region (Vaandrager 1996).

    This aberrant gene rearrangement juxtaposes genes of the immunoglobulin heavy chain (IGH) gene on chromosome 14q32 with the cyclin D1 gene on chromosome 11q13. The juxtaposition of IgH-sequences results in the transcriptional activation of cyclin D1 (De Boer Oncogene 1995; De Boer Blood 1995). Cyclin D1 is involved in the regulation of the G1 progression and G1/S transition of the cell cycle. Translocation does not lead to expression of a fusion protein. In fact, oncogenesis is due to a promoter/enhancer exchange, wherein the immunoglobulin gene enhancer stimulates the expression of cyclin D1. Overexpression of cyclin D1, in turn, accelerates passage of transformed cells through the G1 phase. In the revised WHO-classification, the presence of the t(11;14)(q13;q32) and/or overexpression of cyclin D1 is added as one of the characteristics for mantle cell lymphoma.

    The ~41% of breakpoints clustered in the 1-kb BCL1/MTC locus can be detected by PCR methodology. However, it should be underlined that breakpoints that occur outside the BCL1-MTC locus will not be identified by this particular test. Therefore, a negative result does not completely exclude the presence of a BCL1/JH gene rearrangement in the sample. Results of this test must always be interpreted in the context of morphologic and other relevant data and should not be used alone for a diagnosis of malignancy.

    This test is most useful when confronted with a difficult differential finding that includes mantle cell lymphoma. For instance, a neoplastic B-cell proliferation in tissue, blood, or bone marrow that is difficult to categorize as chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, lymphoma of mucosa-associated lymphoid tissue, or mantle cell lymphoma could readily be classified as the latter if a BCL1/JH gene rearrangement were detected.

    This has important implications, since mantle cell lymphomas are typically more aggressive and have an overall worse prognosis than other low-grade B-cell lymphomas. Since this molecular abnormality is also a tumor-specific marker, it can be used for staging purposes and to monitor specimen for disease relapse after treatment, if their original lymphoma was studied and shown to have a BCL1/JH gene rearrangement.

    Included in this test kit are two master mixes. The BCL1/JH master mix targets the major translocation cluster (MTC) of the BCL1 locus and the joining region of the Ig heavy chain locus. The other master mix, the Specimen Control Size Ladder, targets multiple genes and generates a series of amplicons of 100, 200, 300, 400, and 600 base pairs to ensure that the quality and quantity of input DNA is adequate to yield a valid result. These robust Invivoscribe assays can be used to test DNA extracted from virtually any source.

  • Specimen Requirements

    This assay tests genomic DNA

    • 5cc of peripheral blood, bone marrow biopsy, or bone marrow aspirate anti-coagulated with heparin or EDTA. Ship at ambient temperature; OR
    • Minimum 5mm cube of tissue shipped frozen; or at room temperature or on ice in RPMI 1640; OR
    • 2µg of genomic DNA; OR
    • Formalin-fixed paraffin embedded tissue or slides.

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