Mutations in the First Exon Are Associated with Altered Transcription of c- myc in Burkitt Lymphoma

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Abstract
The c-myc proto-oncogene is involved in chromosomal translocations that are specifically and consistently found in Burkitt lymphoma. Although these translocations are thought to lead to a deregulation of c-myc expression, the structural and functional basis of this phenomenon has not been identified. Mutations in a specific region spanning approximately 70 base pairs and located at the 3' border of the first exon of translocated c-myc alleles were consistently detected in Burkitt lymphoma cells carrying classic (8:14) as well as variant (8:22 and 2:8) translocations. These structural alterations were accompanied by an altered pattern of c-myc transcription, namely, the removal of a block to transcriptional elongation that has been mapped to the same region. Thus, specific c-myc mutations leading to the alleviation of this block to transcriptional elongation may represent a general mechanism causing c-myc activation in Burkitt lymphoma.