AUTHOR=Liang Jianfeng , Zhao Wanni , Lu Changyu , Liu Danni , Li Ping , Ye Xun , Zhao Yuanli , Zhang Jing , Yang Dong 

TITLE=Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00544

DOI=10.3389/fneur.2020.00544

ISSN=1664-2295

ABSTRACT=<p><bold>Background and aims:</bold> The next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 (<italic>n</italic> = 21) and metastatic brain tumor group (<italic>n</italic> = 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) (<italic>P</italic> &lt; 0.05). The mutant genes in metastatic brain tumor group included <italic>ALK, MDM2, ATM, BRCA1, FGFR1, MDM4</italic> and <italic>KRAS</italic>; however, there were no glioma-related mutant genes including <italic>MGMT, IDH1</italic>, IDH2, <italic>1p/19q</italic>, 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, <italic>MDM2, ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET</italic>. The characterizations of <italic>IDH</italic> mutations in the glioma included <italic>IDH1</italic> 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 (<italic>P</italic> &lt; 0.05).</p><p><bold>Conclusion:</bold> 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 <italic>ALK</italic> and <italic>MDM2</italic>, and glioma-related ctDNAs included 1p/19q and <italic>MDM2</italic> followed by frequencies of <italic>ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET</italic>. These ctDNAs might be biomarkers and therapeutic responders in brain tumor.</p>