Which genetic abnormalities are seen in diffuse large B-cell lymphoma (DLBCL)?

Updated: Aug 20, 2020
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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Information obtained from genetic studies performed in DLBCL tumor specimens stresses the complexity in the biology of this disease. DLBCLs express clonally rearranged immunoglobulin H (IgH) genes with somatic mutations in the variable region. For this reason is thought that DLBCL cells are derived from antigen-exposed B-cells. No gene abnormality is pathognomonic for DLBCL. Recurrent translocations involving the BCL6BCL2, and MYC genes have been described in approximately 50% of cases. Chromosomal translocation leading to up-regulation of BCL2 [t(14;18)] is present in 20-30% of DLBCL cases and is especially observed GCB variants. Gene abnormalities in ABC-DLBCL are more complex and include trisomies, deletions, and chromosomal inactivation. [64]

The clinical value of testing for genetic aberrations in DLBCL continues to grow in recognition. A subset of DLBCL patients carrying both c-Myc and Bcl-2 translocations as detected by fluorescence in situ hybridization (FISH) has been identified. These cases, termed double-hit DLBCL, represent approximately 8% of newly diagnosed DLBCL; they exhibit a poor response to standard doses of rituximab chemotherapy regimens and have a poor OS. [65, 66, 67, 68] Moreover, IHC studies have demonstrated that concurrent over-expression of c-Myc and Bcl-2 is associated with a poor clinical outcome. [69, 70] Currently, c-Myc and Bcl-2 cytogenetic studies (ie, FISH) and IHC analysis for Bcl2 and c-Myc over-expression should be performed in DLBCL patients exhibiting a high proliferation index (ie, Ki67 ≥90%).

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