我们对罕见的1级脑脑膜瘤(血管瘤型)和常见的1级脊髓脑膜瘤(参膜型)进行了下一代测序(NGS)分析,并比较了它们的突变谱。使用IonReporter5.16程序(ThermoFisherScientific,沃尔瑟姆,MA).测序分析鉴定出10种新的变体和2种先前报道的变体,它们在这两种肿瘤之间是常见的。九种变体是错误的,其中包括EGFRc.1819_1820insCA中的插入,导致移尸,以及HRAS和HNF1A基因中的单核苷酸缺失,导致这些基因的移码。这些是为两种肿瘤鉴定的常见变体。此外,在这两个肿瘤之间共有10个同义变体和10个内含子变体。在内含子变体中,两个是剪接位点_5'变体(受体位点变体)。典型的血管瘤型肿瘤,有11个新的和6个以前报道的变种是在sammomatous肿瘤中没有发现的;三个变种是同义的,11个是错义突变,还有三个是导致移码的缺失。缺失变体在SMARCB1、CDH1和KDR基因中。相比之下,在假脑膜瘤肿瘤中发现了八个新颖的变体和五个先前报道的变体。在这个肿瘤中,两个变体是同义词:在[(c.3920delT;p。(Ile1307fs)]中导致移码的缺失,并且在APC基因中也发现了两个碱基对的插入和缺失(INDEL)[(c.3986_3987delACinsGT;p。(His1329Arg)]。在我们的发现中,我们已经确认了ALK,VHL,CTNNB1,EGFR,ERBB4,PDGFRA,KDR,SMO,ABL1,HRAS,ATM,HNF1A,FLT3和RB1突变常见于膜膜脑膜瘤和血管瘤瘤。血管瘤(脑)脑膜瘤的典型变体是PIK3CA,KIT,PTPN11,CDH1,SMAD4和SMARCB1;典型的沙膜脑膜瘤的变异是APC,FGFR2,HNF1A,STK11和JAK3。在两种脑膜瘤肿瘤中发现的RET剪接变体(c.1880-2A>C)在单核苷酸多态性数据库(dbSNP)中被报道为可能致病的(rs193922699)。在这两个脑膜瘤中检测到的所有错义变体都在癌症驱动基因中发现。我们在EGFR等基因中发现的八种变异,PDGFRA,SMO,FLT3,PIK3CA,PTPN11、CDH1和RB1是神经胶质瘤驱动基因。我们没有在BRAF等基因中发现任何突变,IDH1,CDKN2A,PTEN,和TP53,它们也被列为神经胶质瘤中的癌症驱动基因。在脑膜瘤中使用NGS技术的突变谱分析可以帮助这些肿瘤的准确诊断和分类以及开发更有效的治疗方法。
We performed the next-generation sequencing (NGS) analysis of a rare grade 1 brain meningioma (angiomatous type) and a common grade 1 spinal meningioma (psammomatous type) and compared their mutation profiling. The data were analysed using the Ion Reporter 5.16 programme (Thermo Fisher Scientific, Waltham, MA). Sequencing analysis identified 10 novel variants and two previously reported variants that were common between these two tumours. Nine variants were missense, which included an insertion in EGFR c.1819_1820insCA, causing frameshifting, and a single nucleotide deletion in HRAS and HNF1A genes, causing frameshifting in these genes. These were common variants identified for both tumours. Also, 10 synonymous variants and 10 intronic variants were common between these two tumours. In intronic variants, two were splice site_5\' variants (acceptor site variants). Typical of the angiomatous type tumour, there were 11 novel and six previously reported variants that were not found in the psammomatous tumour; three variants were synonymous, 11 were missense mutations, and three were deletions causing frameshifting. The deletion variants were in the SMARCB1, CDH1, and KDR genes. In contrast, eight novel and five previously reported variants were found in the psammomatous meningioma tumour. In this tumour, two variants were synonymous: a deletion causing a frameshifting in [(c.3920delT; p. (Ile1307fs)], and a two-base pair insertion and deletion (INDEL) [(c.3986_3987delACinsGT; p. (His1329Arg)] both in the APC gene were also found. Among our findings, we have identified that ALK, VHL, CTNNB1, EGFR, ERBB4, PDGFRA, KDR, SMO, ABL1, HRAS, ATM, HNF1A, FLT3, and RB1 mutations are common for psammomatous meningioma and angiomatous tumours. Variants typical for angiomatous (brain) meningioma are PIK3CA, KIT, PTPN11, CDH1, SMAD4, and SMARCB1; the variants typical for psammomatous meningioma are APC, FGFR2, HNF1A, STK11, and JAK3. The RET splice variant (c.1880-2A>C) found in both meningioma tumours is reported (rs193922699) as likely pathogenic in the Single Nucleotide Polymorphism Database (dbSNP). All missense variants detected in these two meningiomas are found in the cancer-driver genes. The eight variants we found in genes such as EGFR, PDGFRA, SMO, FLT3, PIK3CA, PTPN11, CDH1, and RB1 are glioma-driver genes. We did not find any mutations in genes such as BRAF, IDH1, CDKN2A, PTEN, and TP53, which are also listed as cancer-driver genes in gliomas. Mutation profiling utilising NGS technology in meningiomas could help in the accurate diagnosis and classification of these tumours and also in developing more effective treatments.