CAT #: TRG Clonality

TRG Clonality Assay

  • Description of Test:

    For detection of the vast majority of TRG gene rearrangements, a multiplex master mix targeting the variable (V) and the joining (J) region is used for PCR amplification. Next-generation sequencing of the PCR products is used to identify DNA sequences specific to clonal gene rearrangements. Bioinformatics tools facilitate the characterization of sequences present at greater than 2.5% of the population. These sequences can be used to track specific clonal populations.

  • Overview:

    The human T Cell Receptor Gamma (TRG) locus on chromosome 7 (7q14) includes 14 V (variable region) genes (Group I, II, III, and IV), 5 J (joining region) genes, and 2 C (constant region) genes spread over 200 kilobases.

    Lymphoid cells are different from the other somatic cells in the body, as during development the antigen receptor genes in lymphoid cells (including gene segments within the TRG locus), undergo somatic gene rearrangement. These developmentally regulated, programmed gene rearrangements generate V-J combinations that are unique for each cell.

    Since leukemias and lymphomas originate from the malignant transformation of individual lymphoid cells, all leukemias and lymphomas generally share one or more cell-specific or ‘clonal’ antigen receptor gene rearrangements. Clonality does not always imply malignancy; all results must be interpreted in the context of all of the other available diagnostic criteria. Tests that detect TRG clonal rearrangements can be used to help identify T-cell and certain B-cell malignancies.

    Note: During T-cell ontogeny rearrangement of the TRG locus occurs before rearrangement of the alpha beta loci. So, clonal rearrangements of TRG are often present, commonly detected, and can be tracked in T-cell malignancies involving alpha-beta T-cells. This makes TRG a powerful tool for both clonal and MRD analysis of T-cell and some B-cell tumors.

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References

  1. LC Lawnickie, et al. (2003). The distribution of gene segments in T-cell receptor gamma gene rearrangements demonstrates the need for multiple primer sets. J Mol Diagn. 5:82-87.
  2. Tonegawa S (1983) Somatic Generation of Antibody Diversity. Nature 302:575-581.
  3. van Dongen JJM et al. (2003). 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 17:2257–2317.

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