Characterization of genetic subclonal evolution in pancreatic cancer mouse models.
Characterization of genetic subclonal evolution in pancreatic cancer mouse models.
复制标题
胰腺癌小鼠模型遗传亚克隆进化的表征。
DOI：
10.1038/s41467-019-13100-w
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发表时间：
2019
影响因子：
16.6
通讯作者：
Karchin,Rachel
中科院分区：
文献类型：
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作者：
Niknafs,Noushin;Zhong,Yi;Moral,JohnAlec;Zhang,Lance;Shao,MelodyXiaoshan;Lo,April;Makohon-Moore,Alvin;Iacobuzio-Donahue,ChristineA;Karchin,Rachel
KPC小鼠模型由Kras和Trp53转基因驱动，被认为是对人类胰腺癌生物学的忠实概括。然而，这个模型在多大程度上概括了这种肿瘤类型的亚克隆进化尚不清楚。在这里，我们报告了在肿瘤发生后持续的亚克隆进化的证据，这在很大程度上反映了针对人类胰腺癌已有意义的细胞过程的拷贝数变化。小鼠肿瘤的进化轨迹既有线性的，也有分支的，也有克隆性的混合。我们认为KPC模型及其衍生物作为一个功能系统来模拟肿瘤进化的机制和修饰物的效用尚未被探索。
TheKPCmouse model, driven by theKrasandTrp53transgenes, is well regarded for faithful recapitulation of human pancreatic cancer biology. However, the extent that this model recapitulates the subclonal evolution of this tumor type is unknown. Here we report evidence of continuing subclonal evolution after tumor initiation that largely reflect copy number alterations that target cellular processes of established significance in human pancreatic cancer. The evolutionary trajectories of the mouse tumors show both linear and branching patterns as well as clonal mixing. We propose theKPCmodel and derivatives have unexplored utility as a functional system to model the mechanisms and modifiers of tumor evolution.