Liang Jianfeng, Zhao Wanni, Lu Changyu, Liu Danni, Li Ping, Ye Xun, Zhao Yuanli, Zhang Jing, Yang Dong
Department of Neurosurgery, Peking University International Hospital, Beijing, China.
Department of General Surgery, Beijing Hospital, National Center of Gerontology, Beijing, China.
Front Neurol. 2020 Aug 21;11:544. doi: 10.3389/fneur.2020.00544. eCollection 2020.
The next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited. Based largely on a protocol approved by the institutional review board at Peking University International Hospital, the current retrospective, single-center study was conducted. Genomic DNA was extracted from blood samples or tumor tissues. With the application of NextSeq 500 instrument (Illumina), Sequencing was performed with an average coverage of 550-fold. Paired-end sequencing was employed utilized with an attempt to achieve improved sensitivity of duplicate detection and therefore to increase the detection reliability of possible fusions. A total of 28 patients (21 men and 7 women) with brain tumors in the present study were involved in the study. The patients enrolled were assigned into two groups, including glioma group ( = 21) and metastatic brain tumor group ( = 7). The mean age of metastatic brain tumor group (59.86 ± 8.85 y), (43.65 ± 13.05 y) reported significantly higher results in comparison to that of glioma group (45.3 ± 12.3 years) ( < 0.05). The mutant genes in metastatic brain tumor group included and ; however, there were no glioma-related mutant genes including , IDH2, , and BRAF et al. Interesteringly, only two patient (28.3%) was detected blood ctDNA in metastatic brain tumor group; In contrast, blood ctDNA was found in ten glioma patients (47.6%) including 1p/19q, . The characterizations of mutations in the glioma included mutation (p.R132H) and IDH2 mutation (p.R172K). The mutation rate of IDH in tumor tissues was 37.06 ± 8.32%, which was significantly higher than blood samples ( < 0.05). The present study demonstrated that the mutant genes among glioma and metastatic brain tumors are shown to be different. Moreover, the ctDNAs in the metastatic brain tumors included and , and glioma-related ctDNAs included 1p/19q and followed by frequencies of . These ctDNAs might be biomarkers and therapeutic responders in brain tumor.
在胶质瘤和转移性脑肿瘤中，下一代测序技术及其对循环肿瘤DNA的相关评估在很大程度上仍然有限。本项回顾性单中心研究主要基于北京大学国际医院机构审查委员会批准的方案进行。从血液样本或肿瘤组织中提取基因组DNA。使用NextSeq 500仪器（Illumina）进行测序，平均覆盖度为550倍。采用双端测序以提高重复检测的灵敏度，从而提高可能融合的检测可靠性。本研究共纳入28例脑肿瘤患者（21例男性和7例女性）。纳入的患者分为两组，包括胶质瘤组（n = 21）和转移性脑肿瘤组（n = 7）。转移性脑肿瘤组的平均年龄（59.86±8.85岁），与胶质瘤组（45.3±12.3岁）相比，结果显著更高（P < 0.05）。转移性脑肿瘤组中的突变基因包括[具体基因1]和[具体基因2]；然而，没有发现与胶质瘤相关的突变基因，包括[具体基因3]、IDH2、[具体基因4]和BRAF等。有趣的是，转移性脑肿瘤组中仅2例患者（28.3%）检测到血液ctDNA；相比之下，在10例胶质瘤患者（47.6%）中发现了血液ctDNA，包括1p/19q、[具体基因5]。胶质瘤中[具体基因6]突变的特征包括[具体基因6]突变（p.R132H）和IDH2突变（p.R172K）。肿瘤组织中IDH的突变率为37.06±8.32%，显著高于血液样本（P < 0.05）。本研究表明，胶质瘤和转移性脑肿瘤中的突变基因不同。此外，转移性脑肿瘤中的ctDNA包括[具体基因7]和[具体基因8]，与胶质瘤相关的ctDNA包括1p/19q和[具体基因9]，其次是[具体基因10]的频率。这些ctDNA可能是脑肿瘤的生物标志物和治疗反应指标。
