Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults
Background and aims: The next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited.Methods: Based largely on a protocol approved by the institutional review board at Peking University International...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2020.00544/full |
| _version_ | 1818411992638029824 |
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| author | Jianfeng Liang Wanni Zhao Changyu Lu Danni Liu Ping Li Xun Ye Yuanli Zhao Yuanli Zhao Jing Zhang Dong Yang Dong Yang |
| author_facet | Jianfeng Liang Wanni Zhao Changyu Lu Danni Liu Ping Li Xun Ye Yuanli Zhao Yuanli Zhao Jing Zhang Dong Yang Dong Yang |
| author_sort | Jianfeng Liang |
| collection | DOAJ |
| description | Background and aims: The next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited.Methods: 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.Results: 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 (n = 21) and metastatic brain tumor group (n = 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) (P < 0.05). The mutant genes in metastatic brain tumor group included ALK, MDM2, ATM, BRCA1, FGFR1, MDM4 and KRAS; however, there were no glioma-related mutant genes including MGMT, IDH1, IDH2, 1p/19q, 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, MDM2, ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET. The characterizations of IDH mutations in the glioma included IDH1 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 (P < 0.05).Conclusion: 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 ALK and MDM2, and glioma-related ctDNAs included 1p/19q and MDM2 followed by frequencies of ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET. These ctDNAs might be biomarkers and therapeutic responders in brain tumor. |
| first_indexed | 2024-12-14T10:40:14Z |
| format | Article |
| id | doaj.art-84550a279ead41a7ac0f4ab3c6bce744 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-14T10:40:14Z |
| publishDate | 2020-08-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-84550a279ead41a7ac0f4ab3c6bce7442022-12-21T23:05:44ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-08-011110.3389/fneur.2020.00544524512Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in AdultsJianfeng Liang0Wanni Zhao1Changyu Lu2Danni Liu3Ping Li4Xun Ye5Yuanli Zhao6Yuanli Zhao7Jing Zhang8Dong Yang9Dong Yang10Department of Neurosurgery, Peking University International Hospital, Beijing, ChinaDepartment of General Surgery, Beijing Hospital, National Center of Gerontology, Beijing, ChinaDepartment of Neurosurgery, Peking University International Hospital, Beijing, ChinaHaploX Biotechnology, Shenzhen, ChinaDepartment of Hematology, Tongji Hospital of Tongji University, Shanghai, ChinaDepartment of Neurosurgery, Peking University International Hospital, Beijing, ChinaDepartment of Neurosurgery, Peking University International Hospital, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaHaploX Biotechnology, Shenzhen, ChinaDepartment of Neurosurgery, China-Japan Friendship Hospital, Beijing, ChinaThe 2nd People's Hospital of Tibet Autonomous Region, Lhasa, ChinaBackground and aims: The next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited.Methods: 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.Results: 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 (n = 21) and metastatic brain tumor group (n = 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) (P < 0.05). The mutant genes in metastatic brain tumor group included ALK, MDM2, ATM, BRCA1, FGFR1, MDM4 and KRAS; however, there were no glioma-related mutant genes including MGMT, IDH1, IDH2, 1p/19q, 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, MDM2, ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET. The characterizations of IDH mutations in the glioma included IDH1 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 (P < 0.05).Conclusion: 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 ALK and MDM2, and glioma-related ctDNAs included 1p/19q and MDM2 followed by frequencies of ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET. These ctDNAs might be biomarkers and therapeutic responders in brain tumor.https://www.frontiersin.org/article/10.3389/fneur.2020.00544/fullctDNAbrain tumorsNGSMGMTIDH1/2 |
| spellingShingle | Jianfeng Liang Wanni Zhao Changyu Lu Danni Liu Ping Li Xun Ye Yuanli Zhao Yuanli Zhao Jing Zhang Dong Yang Dong Yang Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults Frontiers in Neurology ctDNA brain tumors NGS MGMT IDH1/2 |
| title | Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults |
| title_full | Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults |
| title_fullStr | Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults |
| title_full_unstemmed | Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults |
| title_short | Next-Generation Sequencing Analysis of ctDNA for the Detection of Glioma and Metastatic Brain Tumors in Adults |
| title_sort | next generation sequencing analysis of ctdna for the detection of glioma and metastatic brain tumors in adults |
| topic | ctDNA brain tumors NGS MGMT IDH1/2 |
| url | https://www.frontiersin.org/article/10.3389/fneur.2020.00544/full |
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