CAT #: IGH Clonality

IGH Clonality Assay

  • Description of Test:

     

    For detection of the vast majority of clonal IGH VH-JH rearrangements, including the associated VH-JH region DNA sequences, a multiplex master mix targeting the conserved framework region 1 (FR1) and the joining 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:

    Lymphoid cells are different from the other somatic cells in the body as during development, the antigen receptor genes in lymphoid cells undergo somatic gene rearrangement.

    The human immunoglobulin heavy chain (IGH) gene locus on chromosome 14 (14q32.3) includes 46-52 functional and 30 non-functional variable (VH) gene segments, 27 functional diversity (DH) gene segments, and 6 functional joining (JH) gene segments spread over 1250 kilobases. During B-cell development, genes encoding the IGH molecules are assembled from multiple polymorphic gene segments that undergo rearrangements and selection. These gene rearrangements of the variable, diversity and joining segments generate VH-DH-JH combinations of unique length and sequence for each cell.

    Since leukemia 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 IGH clonal rearrangements are useful in the characterization and treatment of B- and T-cell malignancies.

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References

  1. Tonegawa S (1983) Somatic Generation of Antibody Diversity. Nature 302:575-581.
  2. Trainor KJ et al. (1990). Monoclonality in B-lymphoproliferative disorders detected at the DNA level. Blood 75:2220-2222.
  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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