Cesarman E, Dalla-Favera R, Bentley D, Groudine M
Department of Pathology, New York University School of Medicine, NY 10016.
Science. 1987 Nov 27;238(4831):1272-5. doi: 10.1126/science.3685977.
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.
c-myc原癌基因参与了在伯基特淋巴瘤中特异性且持续发现的染色体易位。尽管这些易位被认为会导致c-myc表达失调,但这一现象的结构和功能基础尚未明确。在携带经典(8:14)以及变异(8:22和2:8)易位的伯基特淋巴瘤细胞中,始终能检测到位于易位c-myc等位基因第一个外显子3'边界、跨越约70个碱基对的特定区域发生的突变。这些结构改变伴随着c-myc转录模式的改变,即消除了一个已被定位到同一区域的转录延伸阻滞。因此,导致这种转录延伸阻滞缓解的特定c-myc突变可能是伯基特淋巴瘤中引起c-myc激活的普遍机制。