Cory S, Gerondakis S, Adams J M
EMBO J. 1983;2(5):697-703. doi: 10.1002/j.1460-2075.1983.tb01487.x.
The 15:12 chromosome translocations found in most murine plasmacytomas involve the cellular gene (c-myc) homologous to the oncogene (v-myc) of avian retrovirus MC29, Translocation links the c-myc gene of chromosome 15 to the immunoglobulin heavy (H) chain locus of chromosome 12, often within the switch recombination (S) region 5' to the alpha constant region (C alpha) gene. We have investigated c-myc rearrangements in 21 BALB/c plasmacytomas and three B lymphomas by Southern blot analysis. We show that the t(15;12) is a reciprocal chromosome exchange since most tumours contain not only a c-myc gene linked to the S alpha C alpha region but also a separate structure with S mu or S alpha linked to the c-myc 5'-flanking region. Analysis of the two rearrangement products cloned from plasmacytoma J558 suggests that one type of H locus target for translocation is an S alpha region recombined with S mu; two other targets appear to be other switched heavy chain genes and an unrearranged C alpha gene. Nearly all the chromosome 15 breakpoints fall within a 1.1-kb region spanning a 5' c-myc exon; hence scission of the transcriptional unit by translocation can account for the altered c-myc transcription in plasmacytomas. The c-myc breakpoint region lacks substantial homology with S mu or S alpha, arguing against homologous recombination as the translocation mechanism.
在大多数鼠浆细胞瘤中发现的15:12染色体易位涉及与禽逆转录病毒MC29的癌基因(v-myc)同源的细胞基因(c-myc)。易位将15号染色体的c-myc基因与12号染色体的免疫球蛋白重链(H)基因座相连,通常在α恒定区(Cα)基因5'端的开关重组(S)区域内。我们通过Southern印迹分析研究了21个BALB/c浆细胞瘤和3个B淋巴瘤中的c-myc重排。我们发现t(15;12)是一种相互染色体交换,因为大多数肿瘤不仅含有与SαCα区域相连的c-myc基因,还含有一个与c-myc 5'侧翼区域相连的Sμ或Sα的单独结构。对从浆细胞瘤J558克隆的两种重排产物的分析表明,一种易位的H基因座靶标是与Sμ重组的Sα区域;另外两个靶标似乎是其他转换的重链基因和一个未重排的Cα基因。几乎所有15号染色体的断点都落在跨越5' c-myc外显子的1.1 kb区域内;因此,通过易位切断转录单位可以解释浆细胞瘤中c-myc转录的改变。c-myc断点区域与Sμ或Sα缺乏实质性同源性,这表明同源重组不是易位机制。