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Abstract：
In glioma, kinesin family member 23 (KIF23) is up-regulated and plays a vital role in oncogenesis. However, the mechanism underlying KIF23 overexpression in malignant glioma remains to be elucidated. This study aims to find potential causes of KIF23 high expression at genome level. To clarify this issue, we obtained point mutation and copy number alterations (CNAs) of KIF23 in 319 gliomas using whole-exome sequencing. Only two glioma samples with missense mutations in KIF23 coding region were identified, while 7 patients were detected with amplification of KIF23. Additional analysis showed that KIF23 amplification was significantly associated with higher expression of KIF23. Gene ontology analysis indicated that higher copy number of KIF23 was associated TNF-α signaling pathway and mitotic cell circle checkpoint, which probably caused by subsequent upregulated expression of KIF23. Moreover, pan-cancer analysis showed that gaining of copy number was significantly associated with higher expression of KIF23, consolidating our findings in glioma. Thus, it was deduced that elevated KIF23 expression in glioma tended to be caused by DNA copy number amplification, instead of mutation.
摘要：
在神经胶质瘤中，驱动蛋白家族成员23（KIF23）表达上调，在肿瘤发生中起着至关重要的作用。然而,KIF23在恶性神经胶质瘤中过度表达的潜在机制仍有待阐明。本研究旨在寻找KIF23在基因组水平高表达的潜在原因。为了澄清这个问题，我们通过全外显子组测序获得了319例胶质瘤中KIF23的点突变和拷贝数改变(CNAs).仅鉴定出两个在KIF23编码区具有错义突变的神经胶质瘤样本，7例患者检测到KIF23扩增。另外的分析显示KIF23扩增与KIF23的较高表达显著相关。基因本体论分析表明KIF23拷贝数较高与TNF-α信号通路和有丝分裂细胞周期检查点有关,这可能是由随后的KIF23表达上调引起的。此外，泛癌症分析显示,拷贝数的增加与KIF23的高表达显著相关,巩固了我们在神经胶质瘤中的发现.因此，据推测，神经胶质瘤中KIF23表达升高倾向于由DNA拷贝数扩增引起，而不是突变.
