SEQUENCE OF THE MURINE AND HUMAN CELLULAR MYC ONCOGENES AND 2 MODES OF MYC TRANSCRIPTION RESULTING FROM CHROMOSOME-TRANSLOCATION IN B-LYMPHOID TUMORS
SEQUENCE OF THE MURINE AND HUMAN CELLULAR MYC ONCOGENES AND 2 MODES OF MYC TRANSCRIPTION RESULTING FROM CHROMOSOME-TRANSLOCATION IN B-LYMPHOID TUMORS
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DOI：
10.1002/j.1460-2075.1983.tb01749.x
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发表时间：
1983-01-01
期刊：
影响因子：
11.4
通讯作者：
ADAMS, JM
中科院分区：
文献类型：
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作者：
BERNARD, O;CORY, S;ADAMS, JM
15;鼠浆细胞瘤中的8; 12染色体易位和人Burkitt淋巴瘤中的8; 14染色体易位通常将细胞myc癌基因连接到IG H链恒定区的位点（CH位点）。为了阐明c-myc易位是如何以及为什么发生的，对小鼠和人c-myc基因进行测序，并将c-myc转录与c-myc重排相关联。这两个基因都包含3个外显子：第2和第3外显子编码myc多肽，该多肽在哺乳动物和鸟类之间是保守的，特别是在其更基本的C-末端的一半。Southern杂交结果表明，12个Burkitt株系中有4个株系的c-myc基因连锁在CH开关区附近，2个株系的c-myc基因连锁在JH位点附近。因此，IG重组机制可能参与易位，虽然常见的myc断裂点区域周围的外显子1并不像一个开关区。断裂点位于外显子1 5 "处或远离c-myc的肿瘤，其正常c-myc mRNA为2.25和2.4 kb，在5"端不同，而断裂点位于外显子1或内含子1内的肿瘤，其c-myc mRNA发生改变（伯基特细胞系中为2.1 - 2.7 kb），起始于内含子1内。两种类型的mRNA可能产生相同的多肽。由于未易位的c-myc等位基因通常是沉默的，易位到CH位点必须诱导组成型c-myc表达。c-myc mRNA在永生但非致瘤性淋巴母细胞样细胞系中的存在可能暗示c-myc参与永生化步骤。
The 15;12 chromosome translocation in murine plasmacytomas and the 8;14 in human Burkitt lymphomas often link the cellular myc oncogene to the locus for constant regions of Ig H chains (CH locus). To clarify how and why c-myc translocation occurs, the mouse and human c-myc genes were sequenced and c-myc transcription was correlated with c-myc rearrangement. Both genes comprise 3 exons: the 2nd and 3rd encode the myc polypeptide, which is conserved between mammals and birds, particularly in its more basic C-terminal half. Southern blots showed that 4 of 12 Burkitt lines have c-myc linked near CH switch regions and 2 near the joining region (JH) locus. Hence, Ig recombination machinery may participate in translocation, although the common myc breakpoint region around exon 1 does not resemble a switch region. Tumors with breakpoints just 5'' to exon 1, or distant from c-myc, had normal c-myc mRNA of 2.25 and 2.4 kb [kilobases], which differ at their 5'' ends, while tumors with breakpoints within exon 1 or intron 1 had altered c-myc mRNA (2.1-2.7 kb in Burkitt lines), initiated within intron 1. Both types of mRNA probably yielded the same polypeptide. Since the untranslocated c-myc allele was generally silent, translocation to the CH locus must induce constitutive c-myc expression. The presence of c-myc mRNA in immortal but non-tumorigenic lymphoblastoid cell lines may implicate c-myc in an immortalization step.