Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors
Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors
复制标题
B 细胞肿瘤中免疫球蛋白基因上的异质断点参与与 BCL2 5 区域的融合
DOI：
--
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
H. Ohno
中科院分区：
文献类型：
--
作者：
N. Yonetani;C. Ueda;T. Akasaka;M. Nishikori;T. Uchiyama;H. Ohno
BCL 2基因的5′侧翼区（5′-BCL 2）是与免疫球蛋白基因（IG）重排的断点簇。与t（14; 18）（q32; q21）影响BCL 2的3 '区，5′-BCL 2不仅可以与重链基因（IGH）融合，还可以与两个轻链基因（IGL）位点融合。我们在此报告了通过长距离聚合酶链反应扩增的B细胞肿瘤的11个5′-BCL 2/IG连接区的克隆和测序。5′-BCL 2上的断裂点分布在翻译起始位点上游378至2312 bp处，反映了BCL 2调控序列的改变，5′-BCL 2/IGs阳性细胞显示出明显高于t（14;18）阳性细胞的BCL 2表达水平。相反，IG上的断点是可变的。两个5′-BCL 2/IGH和两个5′-BCL 2/IGLK连接发生在连接（J）节段的5 ′，表明错误的变量（V）/多样性（D）/J和V/J重排机制的操作。然而，另外两个5′-BCL 2/IGH连接影响了开关区域，并且在另一种情况下，位于IGLK恒定区下游24 kb的K缺失元件位于5′-BCL 2之后。一个5′-BCL 2/IGLK和两个5′-BCL 2/IGLλ连接涉及内含子区域，其中不发生正常的重组过程。在剩下的一个病例中，5′-BCL 2融合了Vλ基因的3 ′端，该基因位于另一个携带非产生构型的Vλ/Jλ复合物的上游，这表明受体编辑机制可能参与了这种重排。我们的研究揭示了导致BCL 2转录激活的5′-BCL 2/IGs融合基因的异质性解剖，并表明这种特定癌基因/IGs重组形成的机制与t的机制不同（14;18）。
The 5′flanking region of the BCL2 gene (5′‐BCL2) is a breakpoint cluster of rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21) affecting the 3’region of BCL2, 5′‐BCL2 can fuse to not only the heavy chain gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and sequencing of a total of eleven 5′‐BCL2/IGs junctional areas of B‐cell tumors, which were amplified by long‐distance polymerase chain reaction‐based assays. The breakpoints on 5′‐BCL2 were distributed from 378 to 2312 bp upstream of the translational initiation site and, reflecting the alteration of regulatory sequences of BCL2, 5′‐BCL2/IGs‐positive cells showed markedly higher levels of BCL2 expression than those of t(14;18)‐positive cells. In contrast, the breakpoints on the IGs were variable. Two 5′‐BCL2/IGH and two 5′‐BCL2/IGLK junctions occurred 5’of the joining (J) segments, suggesting operation of an erroneous variable (V)/diversity (D)/J and V/J rearrangement mechanism. However, two other 5′‐BCL2/IGH junctions affected switch regions, and the K‐deleting element, which is located 24 kb downstream of the constant region of IGLK, followed the 5′‐BCL2 in another case. One 5′‐BCL2/IGLK and two 5′‐BCL2/IGLλ junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5′‐BCL2 fused 3’of a Vλ, gene that was upstream of another Vλ/Jλ complex carrying a non‐producing configuration, indicating that the receptor editing mechanism was likely involved in this rearrangement. Our study revealed heterogeneous anatomy of the 5′‐BCL2/IGs fusion gene leading to transcriptional activation of BCL2, and suggested that the mechanisms underlying the formation of this particular oncogene/IGs recombination are not identical to those of t(14;18).
登录
查看更多内容
影响因子：
56.9
作者：
TSUJIMOTO, Y;COSSMAN, J;CROCE, CM
通讯作者：
CROCE, CM
434 个连续确定的非霍奇金淋巴瘤标本的细胞遗传学分析：临床相关性。
影响因子：
20.3
作者：
Offit,K;Wong,G;Filippa,DA;Tao,Y;Chaganti,RS
通讯作者：
Chaganti,RS
调节淋巴谱系中的基因组不稳定性和肿瘤形成。
影响因子：
20.3
作者：
Vanasse,GJ;Concannon,P;Willerford,DM
通讯作者：
Willerford,DM
影响因子：
8
作者：
Tashiro,S;Takechi,M;Asou,H;Takauchi,K;Kyo,T;Dohy,H;Kikuchi,M;Kamada,N;Tsujimoto,Y
通讯作者：
Tsujimoto,Y
潜在的 Z-DNA 元件围绕 bcl-2 基因 5 侧翼区域内的染色体易位断点。
影响因子：
8
作者：
Adachi,M;Tsujimoto,Y
通讯作者：
Tsujimoto,Y