The absence of ongoing immunoglobulin gene hypermutation suggests a distinct mechanism for c-myc mutation in endemic Burkitt's lymphoma.
The absence of ongoing immunoglobulin gene hypermutation suggests a distinct mechanism for c-myc mutation in endemic Burkitt's lymphoma.
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持续的免疫球蛋白基因超突变的缺乏表明地方性伯基特淋巴瘤中 c-myc 突变的独特机制。
DOI：
10.1097/00043426-199602000-00006
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Johnston,JM
中科院分区：
文献类型：
--
作者：
Cowley,CG;Carroll,WL;Johnston,JM
目的：伯基特淋巴瘤是一种成熟的、携带免疫球蛋白 (Ig) 的 B 细胞的恶性肿瘤，其特征是 c-myc 和 Ig 基因位点之间的易位。已提出并列 Ig 基因在地方性伯基特淋巴瘤 (eBL) 典型的 c-myc 表达突变和失调中的作用，但从未得到证实。我们的目的是确定 eBL 中 Ig 基因超突变是否正在进行。方法：我们使用逆转录和聚合酶链反应 (PCR) 扩增从 K962 eBL 肿瘤细胞中分离 Ig 重链序列。 PCR 产物连接至 Bluescript II 载体。对多个亚克隆进行了测序，并对可变区进行了比较，以获取正在进行的 Ig 超突变的证据。结果：在所研究的 9 个亚克隆中有 4 个中观察到总共 6 个单碱基替换。四个取代导致氨基酸变化，两个是沉默的。高变区不存在突变聚集，氨基酸置换或链接取代发生率高，所有这些都是 Ig 超突变的特征。观察到的突变发生率与 Taq 聚合酶错误一致。结论：我们的数据表明，在 eBL 肿瘤样本 K962 中，c-myc 突变的机制与引起 Ig 超突变的机制不同。
Purpose: Burkitt's lymphoma is a malignancy of mature, immunoglobulin (Ig)-bearing B cells characterized by translocation between c-myc and Ig gene loci. A role for the juxtaposed Ig genes in the mutation and deregulation of c-myc expression typical of endemic Burkitt's lymphoma (eBL) has been proposed, but never proven. Our objective was to determine whether Ig gene hypermutation is ongoing in eBL.Methods: We isolated Ig heavy-chain sequences from K962 eBL tumor cells using reverse transcription and polymerase chain reaction (PCR) amplification. The PCR product was ligated into Bluescript II vectors. Multiple subclones were sequenced and the variable regions were compared for evidence of ongoing Ig hypermutation.Results: Six total single base substitutions were observed within four of the nine subclones studied. Four substitutions resulted in amino acid changes and two were silent. There was no clustering of mutations in hypervariable regions, or a high incidence of amino acid replacement or link substitutions, all of which are characteristic of Ig hypermutation. The observed mutations occurred at a rate consistent with Taq polymerase error.Conclusions: Our data indicate that in the eBL tumor sample K962, the mechanism underlying c-myc mutation is distinct from that which gives rise to Ig hypermutation.