Altmayer Nora Corinna, Galata Valentina, Warschburger Nadine, Keller Andreas, Meese Eckart, Fischer Ulrike
Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
Chair of Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Oncotarget. 2017 Dec 1;9(2):1803-1812. doi: 10.18632/oncotarget.22804. eCollection 2018 Jan 5.
Gene amplifications are an attribute of tumor cells and have for long time been overlooked in normal cells. A growing number of investigations describe gene amplifications in normal mammalian cells during development and differentiation. Possibly, tumor cells have rescued the gene amplification mechanism as a physiological attribute of stem cells. Here, we investigated human mesenchymal stem cells (hMSCs) for gene amplification using array-CGH, single cell fluorescence hybridization and qPCR. Gene amplifications were detected in mesenchymal stem cells and in mesenchymal stem cells during differentiation towards adipocytes and osteoblasts. Undifferentiated hMSCs harbor 12 amplified chromosomal regions, hMSCs that differentiated towards adipocytes 18 amplified chromosome regions, and hMSCs that differentiate towards osteoblasts 19 amplified regions. Specifically, hMSCs that differentiated towards adipocytes or osteoblasts harbor and amplifications both of which frequently occur in osteosarcoma and liposarcoma that are both of same cell origin. Beside the amplifications, we identified 36 under-replicated regions in undifferentiated and in differentiating hMSC cells.
基因扩增是肿瘤细胞的一个特征，长期以来在正常细胞中被忽视。越来越多的研究描述了正常哺乳动物细胞在发育和分化过程中的基因扩增。肿瘤细胞可能已经将基因扩增机制作为干细胞的一种生理特征保留了下来。在这里，我们使用阵列比较基因组杂交、单细胞荧光杂交和定量聚合酶链反应研究了人间充质干细胞（hMSC）的基因扩增情况。在间充质干细胞以及向脂肪细胞和成骨细胞分化过程中的间充质干细胞中均检测到了基因扩增。未分化的hMSC含有12个扩增的染色体区域，向脂肪细胞分化的hMSC有18个扩增的染色体区域，向成骨细胞分化的hMSC有19个扩增区域。具体而言，向脂肪细胞或成骨细胞分化的hMSC含有扩增区域，这两种扩增在骨肉瘤和脂肪肉瘤中经常出现，而骨肉瘤和脂肪肉瘤都来源于相同的细胞。除了扩增区域，我们还在未分化和正在分化的hMSC细胞中鉴定出36个复制不足的区域。
