Adams J M, Gerondakis S, Webb E, Mitchell J, Bernard O, Cory S
Proc Natl Acad Sci U S A. 1982 Nov;79(22):6966-70. doi: 10.1073/pnas.79.22.6966.
A DNA region not associated with conventional immunoglobulin gene rearrangement is rearranged in many lymphoid tumors. This region, designated here as lymphoid rearranging (LyR) DNA, was cloned from plasmacytoma J558 in which it had recombined 5' to a constant (C) region of the alpha heavy (H) chain gene, C alpha, within a switch (S) region, S alpha, involved in the switching of CH genes. Sequence determination established that LyR DNA had recombined within a S alpha recombination unit. LyR DNA does not originate from the H chain locus, and discordance between LyR DNA and CH copy number in certain lines suggests that LyR DNA probably derives from another chromosome. LyR DNA rearrangement is a characteristic of tumors of mature B cells; it was detected in 24 of 28 plasmacytomas and B-cell lymphomas, usually as LyR-S alpha, but not in 11 Abelson retrovirus-induced lymphomas of B-cell precursors nor detectably in normal B cells. In contrast, rearrangement was observed in only 3 of 18 T-cell lymphomas, and none of seven nonlymphoid lines. Most tumor lines (49 of 52), whether lymphoid or not, contained a low level of polyadenylylated LyR transcript(s), but several new RNA species with differences in their 5' regions appeared in B-cell lines in which LyR DNA was rearranged, suggesting that rearrangement may activate a new promoter or mode of splicing. The results suggest that the LyR-S alpha rearrangement represents a translocation to chromosome 12 that alters expression of LyR-encoded genes; hence, it may have participated in lymphoid tumor oncogenesis.
一个与传统免疫球蛋白基因重排无关的DNA区域在许多淋巴肿瘤中发生重排。该区域在此被命名为淋巴重排（LyR）DNA，是从浆细胞瘤J558中克隆出来的，在该肿瘤中它在一个参与重链（H）基因恒定（C）区α链基因（Cα）5'端的开关（S）区域Sα内发生了重组。序列测定表明LyR DNA在一个Sα重组单元内发生了重组。LyR DNA并非起源于H链基因座，并且在某些细胞系中LyR DNA与CH拷贝数之间的不一致表明LyR DNA可能来源于另一条染色体。LyR DNA重排是成熟B细胞肿瘤的一个特征；在28个浆细胞瘤和B细胞淋巴瘤中有24个检测到了这种重排，通常为LyR-Sα形式，但在11个由Abelson逆转录病毒诱导的B细胞前体淋巴瘤中未检测到，在正常B细胞中也未检测到。相比之下，在18个T细胞淋巴瘤中只有3个观察到重排，在7个非淋巴系细胞中均未观察到重排。大多数肿瘤细胞系（52个中的49个），无论是否为淋巴系，都含有低水平的多聚腺苷酸化LyR转录本，但在LyR DNA发生重排的B细胞系中出现了几种在其5'区域存在差异的新RNA种类，这表明重排可能激活了一个新的启动子或剪接模式。结果表明LyR-Sα重排代表了向12号染色体的易位，这种易位改变了LyR编码基因的表达；因此，它可能参与了淋巴肿瘤的发生。
