Clustered Mutations in the Transcriptional Activation Domain of Myc in 8q24 Translocated Lymphomas and their Functional Consequences

Abstract

Translocation of the Myc gene on chromosome 8q24 to an immunoglobulin gene segment on chromosomes 14q32, 22q11 or 2p12 is believed to be the central event in the pathogenesis of Burkitt’s lymphoma (Dalla-Favera et al. 1982). The molecular heterogeneity of Myc translocations in Burkitt’s lymphoma, suggests that there may be several mechanisms that account for the resulting deregulation of Myc gene transcription, and the consequent abnormalities in cell growth regulation that lead to neoplasia. For example, in many cases of Burkitt’s lymphoma, the transcriptional enhancer of the immunoglobulin heavy chain gene, Eμ, is located on the same chromosome as the translocated Myc gene, suggesting that it may be responsible for activating Myc transcription (Taub et al. 1982). In other cases, however, Eμ and Myc are located on different chromosomes (Rabbitts et al. 1983), and other mechanisms must operate. In sporadic Burkitt’s lymphomas the breakpoints on chromosome 8q24 frequently occur in intron 1 of the Myc gene, separating the oncogene’s regulatory elements from its coding sequences (Pelicci et al. 1986). This suggests that loss of normal regulatory elements may also play a role in abnormal regulation of the translocated oncogene (Taub et al. 1984; Bentley and Groudine 1988; Hann et al. 1988).