Outside North America 
CAT #: 93080020
IdentiClone® BCL1/JH Translocation Assay MegaKit - Gel Detection
Intended Use
The IdentiClone® BCL1/JH Translocation Assay is an in vitro diagnostic product intended for PCR-based detection of BCL1/JH t(11;14)(q13;q32) gene translocations in patients with suspect lymphoproliferations and an be used to:
- Identify BCL1/JH gene translocations highly suggestive of mantle cell lymphoma
- Distinguish mantle cell lymphoma from other neoplastic or benign B-cell proliferations
- Monitor and evaluate disease recurrence
Product Details
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Summary and Explanation of the Test
The BCL1/JH t(11;14)(q13;q32) gene translocation is mainly found in mantle cell lymphoma (MCL) (50-70%), but is also seen in B-prolymphocytic leukemia (B-PLL) (10-20%), plasma cell leukemia (PCL), splenic lymphoma with villous lymphocytes (SLVL), chronic lymphocytic leukemia (CLL) (2-5%), and in multiple myeloma (MM) (20-25%).1 Fluorescence-in-situ-hybridization (FISH) with probes flanking the BCL1/JH translocation breakpoint cluster region (Bcr) on chromosome 11 band q13 revealed that all mantle cell lymphomas (as defined by the REAL-classification) carry the t(11;14)(q13;q32).2,3 The BCL1/JH breakpoints are scattered over a region of 350 kilobases (kb), and approximately 41% of these breakpoints cluster in a locus of only 1 kb referred to as the BCL1 Major Translocation Cluster (MTC) region.3 The BCL1/JH breakpoints clustered in the 1 kb BCL1–MTC locus can be detected by polymerase chain reaction (PCR) methodology.
This aberrant gene translocation juxtaposes genes of the immunoglobulin heavy chain (IGH) joining (JH) region on chromosome 14q32 with the cyclin D1 gene on chromosome 11q13. The juxtaposition of IGH JH sequences results in the transcriptional activation of cyclin D1, which is involved in the regulation of the G1 progression and G1/S transition of the cell cycle.4,5 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. The revised WHO classification includes the presence of the t(11;14)(q13;q32) and/or overexpression of cyclin D1 as one of the characteristics for mantle cell lymphoma.
This test is most useful when confronted with a difficult differential diagnosis that includes MCL. For instance, a neoplastic B-cell proliferation in tissue, blood, or bone marrow that is difficult to categorize as CLL, follicular lymphoma (FL), lymphoma of mucosa-associated lymphoid tissue, or MCL can readily be classified as the latter if a BCL1/JH gene translocation is detected. This has important clinical 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 patients for disease relapse after treatment, if their original lymphoma was studied and shown to have a BCL1/JH gene rearrangement.
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Principles of the Procedure
Polymerase Chain Reaction (PCR)
PCR assays are routinely used for the identification of chromosome translocations. This test targets the MTC region of the BCL1/JH translocation and amplifies genomic DNA between primers that target the BCL1 gene and the conserved joining (JH) regions of the IGH gene (BCL1/JH Tube). Breakpoints that occur outside the MTC 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. DNA from a normal lymphocyte population will also produce a negative result.
Gel Detection
Gel electrophoresis, such as agarose gel electrophoresis or non-denaturing polyacrylamide gel electrophoresisis (PAGE), is commonly used to resolve the different amplicon products based on their size, charge, and conformation. Since DNA is negatively charged, when an electrical potential (voltage) is applied across the gel containing PCR products, the electrical field causes the amplicons to migrate through the gel. Smaller DNA fragments are able to easily migrate through the gel matrix, whereas larger DNA fragments migrate more slowly. This causes a separation of the amplicon products based on size. Ethidium bromide or other DNA intercalating dyes can then be used to stain and detect these products in the gel.
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Specimen Requirements
This assay tests genomic DNA (gDNA) from the following sources:
- 5 cc of peripheral blood, bone marrow biopsy, or bone marrow aspirate anti-coagulated with heparin or EDTA (stored at 2°C to 8°C and shipped at ambient temperature)
- Minimum 5 mm cube of tissue (stored and shipped frozen; or stored and shipped in RPMI 1640 at ambient temperature or on ice)
- 2 µg of gDNA (stored at 2°C to 8°C and shipped at ambient temperature)
- Formalin-fixed paraffin embedded tissue or slides (stored and shipped at ambient temperature)
References
1. Huret, JL. t(11;14)(q13;q32). Atlas Genet. Cytogenet. Oncol. Haematol. May 1998.
2. Coignet, LJA et al. (1996) Blood. 87:1512-1519.
3. Vaandrager, J et al. (1996) Blood. 88:1177-1182.
4. De Boer, CJ et al. (1995) Oncogene. 10:1833-1840.
5. De Boer, CJ et al. (1995) Blood. 86:2715-2723.
Disclaimer
This assay is based on the EuroClonality/BIOMED-2 Concerted Action BMH4-CT98-3936.
Legal Notice
Warranty and Liability
Invivoscribe, Inc. (Invivoscribe®) is committed to providing the highest quality products. Invivoscribe® warrants that the products meet or exceed the performance standards described in the Instructions For Use, as to products with such an insert. If a product is covered by product specifications and does not perform as specified, our policy is to replace the product or credit the full purchase price. No other warranties of any kind, expressed or implied, are provided by Invivoscribe®. Invivoscribe® liability shall not exceed the purchase price of the product. Invivoscribe® shall have no liability for direct, indirect, consequential or incidental damages arising from the use, results of use, or inability to use its products; product efficacy under purchaser controlled conditions in purchaser’s laboratory must be established and continually monitored through purchaser defined and controlled processes including but not limited to testing of positive, negative, and blank controls every time a sample is tested. Ordering, acceptance, and use of product constitutes purchaser acceptance of sole responsibility for assuring product efficacy and purchaser agreement to the limitation of liability set forth in this paragraph.
This product is an in vitro diagnostic product is not available for sale or use within North America.
This product is covered by one or more of the following: European Patent Number 1549764, European Patent Number 2418287, European Patent Number 2460889, Japanese Patent Number 4708029, United States Patent 8859748, United States Patent 10280462, and related pending and future applications. All of these patents and applications are licensed exclusively to Invivoscribe®. Additional patents licensed to Invivoscribe covering some of these products apply elsewhere. Many of these products require nucleic acid amplification methods such as Polymerase Chain Reaction (PCR). No license under these patents to use amplification processes or enzymes is conveyed expressly or by implication to the purchaser by the purchase of this product.
IdentiClone® is a registered trademark of Invivoscribe®.
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