Fischer Ulrike, Backes Christina, Raslan Abdulrahman, Keller Andreas, Meier Carola, Meese Eckart
Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Oncotarget. 2015 Mar 30;6(9):7023-39. doi: 10.18632/oncotarget.3248.
In development of amphibians and flies, gene amplification is one of mechanisms to increase gene expression. In mammalian cells, gene amplification seems to be restricted to tumorigenesis and acquiring of drug-resistance in cancer cells. Here, we report a complex gene amplification pattern in mouse neural progenitor cells during differentiation with approximately 10% of the genome involved. Half of the amplified mouse chromosome regions overlap with amplified regions previously reported in human neural progenitor cells, indicating conserved mechanisms during differentiation. Using fluorescence in situ hybridization, we verified the amplification in single cells of primary mouse mesencephalon E14 (embryonic stage) neurosphere cells during differentiation. In vivo we confirmed gene amplifications of the TRP53 gene in cryosections from mouse embryos at stage E11.5. Gene amplification is not only a cancer-related mechanism but is also conserved in evolution, occurring during differentiation of mammalian neural stem cells.
在两栖动物和果蝇的发育过程中，基因扩增是增加基因表达的机制之一。在哺乳动物细胞中，基因扩增似乎仅限于肿瘤发生以及癌细胞中耐药性的获得。在此，我们报道了小鼠神经祖细胞在分化过程中存在复杂的基因扩增模式，约10%的基因组参与其中。扩增的小鼠染色体区域有一半与先前报道的人类神经祖细胞中的扩增区域重叠，这表明在分化过程中存在保守机制。利用荧光原位杂交技术，我们证实了原代小鼠中脑E14（胚胎期）神经球细胞在分化过程中单个细胞内的扩增。在体内，我们在E11.5期小鼠胚胎的冰冻切片中证实了TRP53基因的基因扩增。基因扩增不仅是一种与癌症相关的机制，而且在进化过程中是保守的，在哺乳动物神经干细胞分化过程中也会发生。
