A middle-aged man presents with a markedly enlarged tonsil and recurrent infections with serum immunoglobulin deficiency. Chromosome analysis demonstrates a translocation between the immunuglobulin heavy chain locus on chromosome 14 and an unidentified gene on chromosome 8. Which of the following is the most likely cause of his phenotype?
This case is an example of Burkitt's lymphoma, which may affect the tonsils or other lymphoid tissues. The translocation places the myc oncogene on chromosome 8 downstream of the very active heavy chain locus on chromosome 14, activating myc gene expression in B cells and their derivatives. The translocation is likely an aberrant form of the normal DNA rearrangements that generate unique heavy chain genes in each B cell. The translocation joins one chromosome 8 to one chromosome 14, leaving their homologues unaffected. The cause for the phenotype must therefore be trans-acting, since cis-acting effects would peain only to the translocated loci and not affect the homologous untranslocated loci. Activation of a tumor-promoting gene (oncogene) on chromosome 8 could produce an enlarged tonsil, while underactivity of immunoglobulin production due to one-half expression could decrease immune function but would not completely ablate the processes in choices a, b, d, and e. At the genetic level, trans-acting events are autosomal dominant in that one of the two homologous loci is abnormal and produces a phenotype. Mutations of cis-acting events must disrupt both homologous loci to produce phenotypes, making them autosomal recessive at the genetic level.
The translocation has deleted constant chain exons on chromosome 14 and prevented heavy chain class switching
The translocation has deleted the interval containing diversity d. and joining (J) regions
The translocation has activated a tumor-promoting gene on chromosome 8
The translocation has deleted the heavy chain constant chain Cu so that virgin B cells cannot produce IgM on their membranes