Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma.
Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma.
复制标题
活化 B 细胞样弥漫性大 B 细胞淋巴瘤中异常的免疫球蛋白类别转换重组和转换易位。
DOI：
10.1084/jem.20062041
复制
发表时间：
2007-03-19
影响因子：
15.3
通讯作者：
Staudt, Louis M.
中科院分区：
文献类型：
--
作者：
Lenz, Georg;Nagel, Inga;Siebert, Reiner;Roschke, Anna V.;Sanger, Warren;Wright, George W.;Dave, Sandeep S.;Tan, Bruce;Zhao, Hong;Rosenwald, Andreas;Muller-Hermelink, Hans Konrad;Gascoyne, Randy D.;Campo, Elias;Jaffe, Elaine S.;Smeland, Erlend B.;Fisher, Richard I.;Kuehl, W. Michael;Chan, Wing C.;Staudt, Louis M.
为了阐明弥漫性大B细胞淋巴瘤(DLBCL)染色体易位的机制，我们研究了这些肿瘤中免疫球蛋白类开关重组(CSR)的性质和范围。我们用Southern blotting检测了DLBCL的活化B细胞样(ABC)、生发中心B细胞样(GCB)和原发纵隔B细胞淋巴瘤(PMBL)亚群的肿瘤样本中合法和不合法的CSR事件。ABC、DLBCL的合法CSR频率低于GCB、DLBCL和PMBL。相反，ABC DLBCL在Switchμ(Sμ)区域的内部缺失频率高于GCB DLBCL和PMBL。在Sγ和其他不合法的开关重组中，ABC DLBCL也有频繁的缺失。序列分析显示，在ABC DLBCL肿瘤克隆中，Sμ正在进行缺失，伴随着正在进行的复制和激活诱导的胞苷脱氨酶依赖的体细胞突变。出乎意料的是，一例来自多条染色体的短片段散布在Sμ内。这些发现表明，ABC DLBCL在CSR调节方面存在异常，可能易发生染色体易位。因此，在涉及BCL6、MYC和新的易位伙伴SPIB的ABC DLBCL中，异常的开关重组是易位的原因。
To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell–like (ABC), germinal center B cell–like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch μ (Sμ) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sγ and other illegitimate switch recombinations. Sequence analysis revealed ongoing Sμ deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase–dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Sμ in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB.
登录
查看更多内容
影响因子：
6
作者：
Martín-Subero, JI;Chudoba, I;Siebert, R
通讯作者：
Siebert, R
DOI：
10.1073/pnas.93.24.13931
发表时间：
1996-11-26
影响因子：
11.1
作者：
Bergsagel, PL;Chesi, M;Kuehl, WM
通讯作者：
Kuehl, WM
影响因子：
30.5
作者：
Manis, JP;Morales, JC;Carpenter, PB
通讯作者：
Carpenter, PB
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
158.5
作者：
Dave, Sandeep S.;Fu, Kai;Staudt, Louis M.
通讯作者：
Staudt, Louis M.