Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors
Abstract Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 4...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00541-w |
| _version_ | 1797276038978338816 |
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| author | Ruichao Chai Songyuan An Han Lin Bo Pang Hao Yan Yun Liu Yilin Wu Long Wang Xing Liu Huiyuan Chen Xueyu Yang Qing Chang Wenqing Jia Yongzhi Wang |
| author_facet | Ruichao Chai Songyuan An Han Lin Bo Pang Hao Yan Yun Liu Yilin Wu Long Wang Xing Liu Huiyuan Chen Xueyu Yang Qing Chang Wenqing Jia Yongzhi Wang |
| author_sort | Ruichao Chai |
| collection | DOAJ |
| description | Abstract Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered. |
| first_indexed | 2024-03-07T15:22:36Z |
| format | Article |
| id | doaj.art-1af3a4888d404ce09eb7a90f348e095f |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-07T15:22:36Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-1af3a4888d404ce09eb7a90f348e095f2024-03-05T17:33:40ZengNature Portfolionpj Precision Oncology2397-768X2024-02-01811910.1038/s41698-024-00541-wSequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumorsRuichao Chai0Songyuan An1Han Lin2Bo Pang3Hao Yan4Yun Liu5Yilin Wu6Long Wang7Xing Liu8Huiyuan Chen9Xueyu Yang10Qing Chang11Wenqing Jia12Yongzhi Wang13Department of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityState Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Jiangsu Simcere Diagnostics Co.,Ltd.Department of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan hospital, Capital Medical UniversityDepartment of Molecular Neuropathology, Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.https://doi.org/10.1038/s41698-024-00541-w |
| spellingShingle | Ruichao Chai Songyuan An Han Lin Bo Pang Hao Yan Yun Liu Yilin Wu Long Wang Xing Liu Huiyuan Chen Xueyu Yang Qing Chang Wenqing Jia Yongzhi Wang Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors npj Precision Oncology |
| title | Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors |
| title_full | Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors |
| title_fullStr | Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors |
| title_full_unstemmed | Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors |
| title_short | Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors |
| title_sort | sequencing of cerebrospinal fluid cell free dna facilitated early differential diagnosis of intramedullary spinal cord tumors |
| url | https://doi.org/10.1038/s41698-024-00541-w |
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