Burkitt's Lymphoma

Burkitt's lymphoma is a solid tumor of B lymphocytes, the lymphocytes that the immune system uses to make antibodies. The genes for making antibodies are located on chromosomes 14 (the heavy [H] chains), 2 (kappa light chains), and 22 (lambda light chains). These genes are expressed only in B lymphocytes because only B cells have the necessary transcription factors for the promoters and enhancers needed to turn these antibody genes "on".

In most (approximately 90%) of the cases of Burkitt's lymphoma, a reciprocal translocation (designated t(8;14) has moved the proto-oncogene c-myc from its normal position on chromosome 8 to a location close to the enhancers of the antibody heavy chain genes on chromosome 14.

In all the other cases, c-myc has been translocated close to the antibody genes on chromosome 2 or 22. In every case, c-myc now finds itself in a region of vigorous gene transcription, and it may simply be the overproduction of the c-myc product (a transcription factor essential for mitosis of mammalian cells) that turns the lymphocyte cancerous. Uncontrolled mitosis of this cell results in a clone of cancer cells, Burkitt's lymphoma. Many other human cancers involve chromosome aberrations, such as translocations, at the loci of known proto-oncogenes.

Here is an actual karyotype (courtesy of Janet Finan and C. M. Croce) of a cell from the tumor of a patient with Burkitt's lymphoma. The long (q) arm of the resulting chromosome 8 is shorter (8q) than its normal homologue; the long arm of translocated chromosome 14 longer (14q+).

The heavy chain gene locus on chromosome 14 is a dangerous place. Several other proto-oncogenes produce cancerous B cells — leukemias, lymphomas, and multiple myelomas — when translocated into this locus.

Example: BCL-2

The risk of translocations involving the heavy chain gene locus is probably especially high because breaks in its DNA occur naturally during the synthesis of antibodies — Link to class switch recombination (CSR).

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19 November 2013