Polyclonal structure of intestinal adenomas in Apc-(Min)/+ mice with concomitant loss of Apc(+) from all tumor lineages
Polyclonal structure of intestinal adenomas in Apc-(Min)/+ mice with concomitant loss of Apc(+) from all tumor lineages
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DOI：
10.1073/pnas.94.25.13927
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Dove, WF
中科院分区：
文献类型：
--
作者：
Merritt, AJ;Gould, KA;Dove, WF
当肿瘤在肠上皮中形成时，了解它们是否涉及单个启动的体细胞克隆非常重要。已知人类和小鼠的晚期癌症是单克隆的。然而，肿瘤发生的早期阶段可能涉及属于上皮内单独体细胞克隆的细胞之间的相互作用。早期肿瘤的克隆性已经在具有肠道肿瘤遗传倾向的小鼠中进行了研究。对普遍表达的细胞谱系标记物嵌合的 Min（多发性肠肿瘤）小鼠的分析表明，正常的肠隐窝是单克隆的，但肠腺瘤通常具有多克隆结构，即使非常小，也呈现出由至少两个体细胞谱系组成的单个局灶性腺瘤。此外，在这些多克隆腺瘤中，所有肿瘤谱系经常丢失野生型 Ape 等位基因。这些观察结果可以通过上皮内克隆相互作用的几种模型来解释，从高肿瘤潜力区域内的被动融合到主动克隆合作的要求。
When tumors form in intestinal epithelia, it is important to know whether they involve single initiated somatic clones. Advanced carcinomas in humans and mice are known to be monoclonal. However, earlier stages of tumorigenesis may instead involve an interaction between cells that belong to separate somatic clones within the epithelium. The clonality of early tumors has been investigated in mice with an inherited predisposition to intestinal tumors. Analysis of Min (multiple intestinal neoplasia) mice chimeric for a ubiquitously expressed cell lineage marker revealed that normal intestinal crypts are monoclonal, but intestinal adenomas frequently have a polyclonal structure, presenting even when very small as single, focal adenomas composed of at least two somatic lineages. Furthermore, within these polyclonal adenomas, all tumor lineages frequently lose the wild-type Ape allele. These observations can be interpreted by several models for clonal interaction within the epithelium, ranging from passive fusion within regions of high neoplastic potential to a requirement for active clonal cooperation.