目的:原发性颅内粘液乳头状室管膜瘤(MPE)非常罕见。为了确定颅内MPE的基因组变化,我们通过下一代DNA测序分析了其突变模式。
方法:使用离子质子仪器上的离子PIv3芯片对肿瘤DNA进行测序,并通过离子报告5.6分析数据。
结果:在该肿瘤中,NGS使用IonPIv3芯片生成6,298,354个映射读段。每个扩增子的平均读段为29,365,100%的扩增子具有至少500个读段,并且扩增子端到端读段为97.58%。在这个肿瘤中,NGS数据分析确定了12种变体,其中两个是错义突变,7个是同义突变,3个是内含子变异.错义突变c.395G>A;在IDH1基因的外显子4中,并且在c.215C>G中出现错义突变;在TP53基因的外显子4中发现了这种肿瘤。在这种肿瘤中发现的已知同义突变是,在c.1953G>A的FGFR3外显子14中;在c.1701A>G的PDGFRA外显子12中;在PDGFRAc.2472C>T的外显子18中;在c.2361G>A的EGFR外显子20中;在c.2107G>T的RET外显子13中;在c.4479G>A的APC的外显子16中;以及在c.345345此外,在KDR中鉴定出一个已知的内含子变异体,在FLT3中鉴定出一个已知的受体位点剪接变异体(rs2491231),并在CSF1R基因的3'-UTR中鉴定出一个SNP(rs2066934).除了,IDH1变异的频率,其他变体的频率很高,所有这些突变的p值都很显著,Phred评分都很高.
结论:之前通过NGS分析未在粘液毛细血管I级室管膜瘤中检测到该肿瘤中报告的变异,因此我们首次在该病例中报告了这些变异。
OBJECTIVE: Primary intracranial myxopapillary ependymomas (MPE) are very rare. In order to determine genomic changes in an intracranial MPE, we analyzed its mutation patterns by next generation DNA sequencing.
METHODS: Tumor DNA was sequenced using an Ion PI v3 chip on Ion Proton instrument and the data were analyzed by Ion Reporter 5.6.
RESULTS: In this tumor, NGS generated 6,298, 354 mapped reads using the Ion PI v3 Chip. The average reads per amplicon was 29,365, 100% of amplicons had at least 500 reads and the amplicons read end-to-end were 97.58%. In this tumor, NGS data analysis identified 12 variants, of which two were missense mutations, seven were synonymous mutations and three were intronic variants. Missense mutation in c.395G>A; in exon 4 of the IDH1 gene, and a missense mutation in c.215C>G; in exon 4 of the TP53 gene were found in this tumor were previously reported. The known synonymous mutations were found in this tumor were, in exon 14 of FGFR3 in c.1953G>A; in exon 12 of PDGFRA in c.1701A>G; in exon 18 of PDGFRA c.2472C>T; in exon 20 of EGFR in c.2361G>A; in exon 13 of RET in c.2307G>T; in exon 16 of APC in c.4479G>A; and in exon 2 of MET in c.534C>T. Additionally, a known intronic variant was identified in KDR and a known acceptor site splice variant in FLT3 (rs2491231) and a SNP in the 3 \' -UTR of the CSF1R gene (rs2066934) were also identified. Except, the frequency of IDH1 variant, the frequencies of other variants were high, and the p-values were significant and Phred scores were high for all of these mutations.
CONCLUSIONS: The variants reported in this tumor have not been detected in myxopapillary grade I ependymoma tumor by NGS analysis previously and we therefore report these variants in this case for the first time.