High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas
High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas
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DOI：
10.1158/0008-5472.can-03-3885
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发表时间：
2004-07-01
期刊：
影响因子：
11.2
通讯作者：
Morse, HC
中科院分区：
文献类型：
--
作者：
Shin, MS;Fredrickson, TN;Morse, HC
人类B细胞淋巴瘤通常与激活原癌基因的染色体易位引起的特定遗传变化有关。对于表达鼠白血病病毒的小鼠淋巴瘤，诱变前病毒插入被认为起类似的作用。在这里，我们报告的研究旨在确定是否特定的逆转录病毒整合位点可能与一个特定的小鼠B细胞淋巴瘤的子集，如果与这些网站相关的基因的表达经常改变。我们研究了NFS. V+小鼠的脾边缘区淋巴瘤（MZL），这些小鼠在表现出从低到高的频繁进展方面是不寻常的，可能允许将癌症基因分配到起始和进展的过程。我们使用反向PCR克隆和分析212个逆转录病毒整合位点从43 MZL在不同阶段的进展。62个标记的共同整编地点，包括31个以前标记过的地点。在新的常见整合位点中，有7个是MZL独有的。使用微阵列和实时定量PIER分析，我们定义了与疾病进展相关的Gfi1、Sox 4、Brca 2、Snf1lk、Nfkb1、Pou2af 1、Prdm 1、Stat6和Blnk基因表达的差异模式。Gfi1的高表达将MZL与其他淋巴瘤类型区分开来。因此，前病毒标签和基因表达分析的结合使用提供了一种强有力的方法来理解在肿瘤发生中协作的基因。
Human B-cell lymphomas are frequently associated with specific genetic changes caused by chromosomal translocations that activate protooncogenes. For lymphomas of mice expressing murine leukemia virus, mutagenic proviral insertions are thought to play a similar role. Here we report studies designed to determine whether specific retroviral integration sites might be associated with a specific subset of mouse B-cell lymphomas and if the genes associated with these sites are regularly altered in expression. We studied splenic marginal zone lymphomas (MZL) of NFS.V+ mice that are unusual in exhibiting frequent progression from low to high grade, potentially allowing assignment of cancer genes to processes of initiation and progression. We used inverse PCR to clone and analyze 212 retroviral integration sites from 43 MZL at different stages of progression. Sixty-two marked common integration sites and included 31 that had been marked previously. Among the new common integration sites, seven were unique to MZL. Using microarrays and real-time quantitative PIER analysis, we defined differential patterns of gene expression in association with disease progression for Gfi1, Sox4, Brca2, Snf1lk, Nfkb1, Pou2af1, Prdm1, Stat6, and Blnk. Heightened expression of Gfi1 distinguishes MZL from other lymphoma types. The combined use of proviral tagging and analyses of gene expression thus provides a powerful approach to understanding of genes that collaborate in tumorigenesis.