Insertional hypermutation in mineral oil-induced plasmacytomas.
Insertional hypermutation in mineral oil-induced plasmacytomas.
复制标题
矿物油诱导的浆细胞瘤中的插入超突变。
DOI：
10.1002/eji.201344322
复制
发表时间：
2014
影响因子：
5.4
通讯作者：
Wabl,Matthias
中科院分区：
文献类型：
--
作者：
Knittel,Gero;Metzner,Mirjam;Beck-Engeser,Gabriele;Kan,Ada;Ahrends,Tomasz;Eilat,Dan;Huppi,Konrad;Wabl,Matthias
除非受到慢性炎症因子（如矿物油）的刺激，浆细胞肿瘤在年轻BALB/c小鼠中是罕见的。这就提出了一个问题：炎症组织提供了什么来促进突变？诱变的本质是什么？我们确定矿物油诱导的浆细胞瘤产生大量内源性后转录因子-嗜生态和多嗜性小鼠白血病病毒和内源性A颗粒。因此，浆细胞瘤的形成可能部分是由炎症诱导或帮助这些逆转录因子的重新插入引起的。我们在单个浆细胞瘤中发现了多达10个新的插入，大多数是在具有常见逆转录病毒整合位点的基因中。在细胞培养过程中，肿瘤从实体瘤进化到几代的过程中还伴随着其他整合。肿瘤基因重新整合的高频率表明，内源性逆转录因子是BALB/c小鼠浆细胞瘤形成和进展的共同原因。
Unless stimulated by a chronic inflammatory agent, such as mineral oil, plasma cell tumors are rare in young BALB/c mice. This raises the questions: What do inflammatory tissues provide to promote mutagenesis? And what is the nature of mutagenesis? We determined that mineral oil‐induced plasmacytomas produce large amounts of endogenous retroelements—ecotropic and polytropic murine leukemia virus and intracisternal A particles. Therefore, plasmacytoma formation might occur, in part, by de novo insertion of these retroelements, induced or helped by the inflammation. We recovered up to ten de novo insertions in a single plasmacytoma, mostly in genes with common retroviral integration sites. Additional integrations accompany tumor evolution from a solid tumor through several generations in cell culture. The high frequency of de novo integrations into cancer genes suggests that endogenous retroelements are coresponsible for plasmacytoma formation and progression in BALB/c mice.