Genomics of Burkitt lymphoma

The malignant cells of Burkitt lymphoma show a mature B-cell phenotype and are negative for the enzyme terminal deoxynucleotidyl transferase. These malignant cells usually express surface immunoglobulin (Ig), most bearing a clonal surface IgM with either kappa or lambda light chains. A variety of additional B-cell markers (e.g., CD19, CD20, CD22) are usually present, and most childhood Burkitt lymphomas express CD10.[1]

Burkitt lymphoma expresses a characteristic chromosomal translocation, usually t(8;14) and more rarely t(8;22) or t(2;8). Each of these translocations juxtaposes the MYC oncogene and the immunoglobulin locus (IG, mostly the IGH locus) regulatory elements, resulting in the inappropriate expression of MYC, a gene involved in cellular proliferation.[2,3] The presence of one of the variant translocations t(2;8) or t(8;22) does not appear to affect response or outcome.[4,5]

Mapping of IGH-translocation breakpoints demonstrated that IG::MYC translocations in sporadic Burkitt lymphoma most commonly occur through aberrant class-switch recombination and less commonly through somatic hypervariant. Translocations resulting from aberrant variable, diversity, and joining (VDJ) gene segment recombinations are rare.[6] These findings are consistent with a germinal center derivation of Burkitt lymphoma.

While MYC translocations are present in all Burkitt lymphoma, cooperating genomic alterations appear to be required for lymphoma development. Some of the more commonly observed recurring variants that have been identified in Burkitt lymphoma in pediatric and adult cases are listed below. The clinical significance of these variants for pediatric Burkitt lymphoma remains to be elucidated.

A study that compared the genomic landscape of endemic Burkitt lymphoma with the genomics of sporadic Burkitt lymphoma found the expected high rate of Epstein-Barr virus (EBV) positivity in endemic cases, with much lower rates in sporadic cases. There was general similarity between the patterns of variants for endemic and sporadic cases and for EBV-positive and EBV-negative cases. However, EBV-positive cases showed significantly lower variant rates for selected genes/pathways, including SMARCA4, CCND3, TP53, and apoptosis.[5]

Cytogenetic evidence of MYC rearrangement is the gold standard for diagnosis of Burkitt lymphoma. For cases in which cytogenetic analysis is not available, the World Health Organization (WHO) has recommended that the Burkitt-like diagnosis be reserved for lymphoma resembling Burkitt lymphoma or with more pleomorphism, large cells, and a proliferation fraction (i.e., MIB-1 or Ki-67 immunostaining) of 99% or greater.[1] BCL2 staining by immunohistochemistry is variable. The absence of a translocation involving the BCL2 gene does not preclude the diagnosis of Burkitt lymphoma and has no clinical implications.[12]