Which genetic abnormalities are seen in DLBCL?

Updated: Jun 12, 2019
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

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 BCL6, BCL2, 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. [47, 48]

The clinical value of testing for genetic aberrations in DLBCL continues to grow in recognition. Recently, a subset of DLBCL patients carrying both c-Myc and Bcl-2 translocations as detected by fluorescence in situ hybridization (FISH) were identified. Those patients are known as having “double-hit DLBCL” which represents approximately 8% of newly diagnosed DLBCL patients. It exhibits a poor response to standard doses of rituximab chemotherapy regimens and has a poor OS. [49, 50, 51, 52] Moreover, IHC studies have demonstrated that concurrent over-expression of c-Myc and Bcl-2 is associated with a poor clinical outcome. [53, 54] 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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