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小鼠浆细胞瘤中的(6;15)易位变体发生在免疫球蛋白κ基因附近,但远离myc癌基因。

Variant (6 ; 15) translocation in a murine plasmacytoma occurs near an immunoglobulin kappa gene but far from the myc oncogene.

作者信息

Webb E, Adams J M, Cory S

出版信息

Nature. 1984;312(5996):777-9. doi: 10.1038/312777a0.

Abstract

Chromosome translocations in B-lymphoid tumours are providing intriguing insights and puzzles regarding the role of immunoglobulin genes in the activation of the myc oncogene (reviewed in refs 1, 2). The 15 ; 12 translocations found in most murine plasmacytomas and the analogous 8 ; 14 translocation in human Burkitt's lymphomas involve scissions of murine chromosome 15 (human chromosome 8) near the 5' end of the c-myc gene and subsequent fusion near an immunoglobulin heavy-chain gene. The less well characterized 'variant' translocations found in about 15% of such tumours also involve the myc-bearing chromosome band, but exchange occurs with a chromosome bearing an immunoglobulin light-chain locus--in mice, the kappa-chain locus bearing chromosome 6 (refs 3-5) and, in man, chromosome 2 (or 22), at the same band at which the kappa (or lambda) locus lies (reviewed in ref. 1). The Burkitt variant translocations involve scissions 3' of c-myc; one 8 ; 22 translocation placed the C lambda locus just 3' of c-myc, but usually the chromosome 8 breakpoint is a greater, but unknown, distance away from c-myc, more than 20 kilobases (kb) in one 8 ; 2 translocation involving the C kappa gene. Little is known about the murine 6 ; 15 translocations, although a C kappa gene cloned from one plasmacytoma (PC7183) is linked, via chromosome 12 sequences, to an unidentified region of chromosome 15 (ref. 11). We describe here the chromosome fusion region from plasmacytoma ABPC4, which displays the typical reciprocal 6;15 translocations. We find that the chromosome 6 breakpoint is near C kappa but, unlike those in the heavy-chain locus, not at a position where immunoglobulin genes normally recombine. Moreover, the chromosome 15 sequences involved in the ABPC4 translocation are not derived from the vicinity of c-myc.

摘要

B淋巴细胞肿瘤中的染色体易位为免疫球蛋白基因在myc癌基因激活中的作用提供了引人入胜的见解和谜题(参考文献1、2中有综述)。在大多数鼠浆细胞瘤中发现的15;12易位以及人类伯基特淋巴瘤中类似的8;14易位,涉及鼠染色体15(人类染色体8)在c-myc基因5'端附近的断裂,随后在免疫球蛋白重链基因附近融合。在约15%的此类肿瘤中发现的特征不太明确的“变异”易位也涉及携带myc的染色体带,但交换发生在携带免疫球蛋白轻链基因座的染色体上——在小鼠中,携带κ链基因座的染色体6(参考文献3 - 5),在人类中,是染色体2(或22),在κ(或λ)基因座所在的同一带(参考文献1中有综述)。伯基特变异易位涉及c-myc的3'端断裂;一个8;22易位将Cλ基因座置于c-myc的3'端,但通常染色体8的断点距离c-myc更远且未知,在一个涉及Cκ基因的8;2易位中超过20千碱基(kb)。关于鼠6;15易位知之甚少,尽管从一个浆细胞瘤(PC7183)克隆的Cκ基因通过染色体12序列与染色体15的一个未鉴定区域相连(参考文献11)。我们在此描述浆细胞瘤ABPC4的染色体融合区域,其显示典型的相互6;15易位。我们发现染色体6的断点靠近Cκ,但与重链基因座中的断点不同,不在免疫球蛋白基因正常重组的位置。此外,ABPC4易位中涉及的染色体15序列并非来自c-myc附近。

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