What is the role of genetics in the etiology of Burkitt lymphoma?

Updated: Dec 20, 2019
  • Author: Ali H Kanbar, MD; Chief Editor: Emmanuel C Besa, MD  more...
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The classic t(8;14)(q24;q32) reciprocal translocation (85% of cases) results in the transposition of the c-myc proto-oncogene on chromosome 8 with one of the immunoglobulin heavy chain genes on chromosome 14, which results in activation of the c-myc gene and is considered responsible for tumor proliferation. Translocation t(8;14) is the most common, present in 80% of Burkitt lymphoma  cases. In all the other cases, c-myc has been translocated close to one of the immunoglobulin light chain genes on chromosome 2 (kappa light chain) [t(8;2)] or 22 (lambda light chain) [t(8;22)].

Overproduction of the c-myc product may change the lymphocytes into cancer cells, but other gene mutations may be responsible for the progression of Burkitt lymphoma. [6] Abnormalities in the p53 gene and in death-associated protein kinase (DAP-kinase) has been shown to contribute to decreased apoptosis and to the pathogenesis of the disease. [14, 15]

C-myc is a leucine zipper transcription factor that affects different pathways regulating cell cycle, growth, adhesion, differentiation, and apoptosis. [16, 17] It is overexpressed via its juxtaposition with immunoglobulin gene enhancers. Genes like cyclin D2, TRAP1, and HLA-DRB1 are induced with c-myc overexpression, whereas others like p21 and platelet-derived growth factor receptor-alpha (PDGFR-alpha) are consistently repressed, possibly playing a role in the pathogenesis of Burkitt lymphoma. [18]

E2F1 is a member of the E2F family of transcription factors that is involved in regulation of cell growth. Interestingly, in recent years, E2F1 was found to be overexpressed in most sporadic cases of Burkitt lymphoma. Furthermore, reduction of E2F1 expression led to decreased growth capacity in sBL cells in vitro. [19]

Mutations in the ID3 gene have been found in 34-68% of Burkitt lymphomas. The role of these inactivating ID3 mutations may be to significantly amplify the actions of the c-myc–immunoglobulin translocation, increas cell cycle progression and cellular proliferation in Burkitt lymphoma cells, [20, 21]  In a study that involved genetic sequencing of 59 Burkitt lymphoma tumors, ID3 was one of 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. [20]  

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