Adams J M, Cory S
Proc R Soc Lond B Biol Sci. 1985 Oct 22;226(1242):59-72. doi: 10.1098/rspb.1985.0079.
The chromosome translocations characteristic of certain B lymphoid tumours associate the myc oncogene and immunoglobulin loci. The typical t(12;15) in murine plasmacytomas and analogous t(14;8) in Burkitt lymphomas couple the myc coding region to one of the switch recombination regions within the immunoglobulin heavy (H) chain locus; hence the switch machinery may promote some translocations. Significantly, translocation induces constitutive myc expression, the untranslocated myc allele remaining silent. The predilection for breakpoints near the 5' end of the c-myc gene may reflect selection for altered myc regulation. In most tumours, the stimulatory effect of the H locus context is not understood, but an H locus enhancer participates in some tumours, including one displaying a novel transposition. The variant (6;15) translocations found in about 15% of plasmacytomas involve the myc band and the region of chromosome 6 where the kappa locus lies. The t(6;15) is shown here to represent an exchange between C kappa and a chromosome 15 locus (designated pvt-1) which lies unexpectedly far from c-myc. The association of myc expression with pvt-1 alterations suggest that myc can be activated at a distance. Myc has also been implicated in some T lymphomas by detection of proviral inserts near myc and also, surprisingly, within the pvt-1 locus. Inserts near myc appear to activate its expression via the retroviral enhancer.
某些B淋巴细胞肿瘤特有的染色体易位将myc癌基因与免疫球蛋白基因座联系起来。小鼠浆细胞瘤中典型的t(12;15)以及伯基特淋巴瘤中类似的t(14;8),将myc编码区与免疫球蛋白重链(H)基因座内的一个开关重组区相连;因此,开关机制可能促进了一些易位。值得注意的是,易位会诱导myc的组成型表达,未易位的myc等位基因则保持沉默。c-myc基因5'端附近的断点偏好可能反映了对myc调控改变的选择。在大多数肿瘤中,H基因座背景的刺激作用尚不清楚,但一个H基因座增强子参与了一些肿瘤,包括一个显示出新型转座的肿瘤。在大约15%的浆细胞瘤中发现的变异型(6;15)易位涉及myc带和6号染色体上kappa基因座所在的区域。本文显示t(6;15)代表C kappa与15号染色体上一个位点(命名为pvt-1)之间的交换,该位点意外地远离c-myc。myc表达与pvt-1改变的关联表明myc可以在远距离被激活。通过检测myc附近以及令人惊讶的是在pvt-1基因座内的前病毒插入片段,myc也与一些T淋巴瘤有关。myc附近的插入片段似乎通过逆转录病毒增强子激活其表达。