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Gene amplifications in tumor cells:newly developed or adapted from normal cells?

肿瘤细胞中的基因扩增：新开发的还是从正常细胞改造而来？

基本信息

批准号：
151348859
负责人：
Privatdozentin Dr. Ulrike Fischer
金额：
--
依托单位：
Institut für Humangenetik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/151348859?language=en
关键词：
Gene amplifications tumor cells newly

项目摘要

Gene amplification is a hallmark of human tumors and has an impact on patients prognosis in several cancers. As of now, gene amplifications during normal development are only known from amphibians and flies. The data from my first grant period show that gene amplifications can also occur in normal mammalian cells. Specifically, during differentiation of human and mouse neural progenitor cells genome-wide gene amplifications were detectable. Notably, about 50% of the mouse amplified chromosome regions were also detected in human. In addition, many of these amplified chromosomal regions overlap with chromosomal regions amplified in human glioblastoma. In contrast to gene amplifications in human tumor cells, gene amplifications of human and mouse neural progenitor cells appear to occur only during a small time-window in a small number of cells. Based on these data, the following questions arise:Are gene amplifications detectable in other cells than neural stem cells during differentiation? Is there evidence for gene amplification being a frequent phenomenon during differentiation in mammalian cells? What is the fate of the amplified DNA and of the cells that harbor amplifications? What is the genomic organization of the amplified DNA in neural progenitor cells and can known models of the origin of gene amplification be supported or disproved by these genomic structures?

基因扩增是人类肿瘤的一个标志，对几种癌症患者的预后有影响。到目前为止，在正常发育过程中的基因扩增只在两栖动物和苍蝇中发现。从我的第一个资助期的数据表明，基因扩增也可以发生在正常的哺乳动物细胞。具体而言，在人类和小鼠神经祖细胞的分化过程中，可检测到全基因组基因扩增。值得注意的是，约50%的小鼠扩增的染色体区域也在人类中检测到。此外，这些扩增的染色体区域中的许多与人胶质母细胞瘤中扩增的染色体区域重叠。与人类肿瘤细胞中的基因扩增相反，人类和小鼠神经祖细胞的基因扩增似乎仅在少量细胞中的小时间窗期间发生。基于这些数据，出现了以下问题：基因扩增检测在其他细胞比神经干细胞在分化过程中？是否有证据表明基因扩增是哺乳动物细胞分化过程中的一种常见现象？扩增的DNA和含有扩增产物的细胞的命运是什么？神经祖细胞中扩增的DNA的基因组结构是什么？这些基因组结构能支持或反驳基因扩增起源的已知模型吗？