PDF(Pubmed)
Abstract：
OBJECTIVE: Although cerebrospinal fluid (CSF)-based liquid biopsy was proved to be practical in molecular analysis of intracranial gliomas, liquid biopsy of primary intramedullary astrocytoma was rarely reported. Given the distinct genomic profiles between primary intramedullary glioma and intracranial astrocytoma, whether the feasibility of CSF-based molecular analysis of intracranial gliomas can be replicated in primary spinal cord astrocytoma needs to be investigated. The aim of this pilot study is to evaluate the feasibility of molecular analysis of primary intramedullary astrocytoma through sequencing CSF-derived circulating tumor DNA (ctDNA).
METHODS: Two grade IV diffuse midline gliomas, 1 grade II, and 1 grade I astrocytoma were included. Intraoperative collection of peripheral blood and CSF samples was conducted, along with postoperative collection of matched tumor tissues. A panel covering the 1,021 most common driver genes of solid tumors was used for targeted DNA sequencing.
RESULTS: CSF-derived ctDNA was detected in 3 CSF samples (2 grade IV diffuse midline gliomas and 1 grade I astrocytoma), 5 mutations were found in both tumor tissues and CSF samples, while 11 mutations and 20 mutations were detected exclusively in tumor tissues and CSF samples, respectively. Importantly, hotspot genetic alterations, including H3F3A K28M, TP53, and ATRX, were identified in CSF and the average mutant allele frequency was often higher in CSF than in tumor tissues.
CONCLUSIONS: CSF-based liquid biopsy showed potential feasibility for molecular analysis of primary intramedullary astrocytoma through sequencing of ctDNA. This approach may assist in diagnosis and prognostic evaluation of this rare spinal cord tumor.
METHODS: Two grade IV diffuse midline gliomas, 1 grade II, and 1 grade I astrocytoma were included. Intraoperative collection of peripheral blood and CSF samples was conducted, along with postoperative collection of matched tumor tissues. A panel covering the 1,021 most common driver genes of solid tumors was used for targeted DNA sequencing.
RESULTS: CSF-derived ctDNA was detected in 3 CSF samples (2 grade IV diffuse midline gliomas and 1 grade I astrocytoma), 5 mutations were found in both tumor tissues and CSF samples, while 11 mutations and 20 mutations were detected exclusively in tumor tissues and CSF samples, respectively. Importantly, hotspot genetic alterations, including H3F3A K28M, TP53, and ATRX, were identified in CSF and the average mutant allele frequency was often higher in CSF than in tumor tissues.
CONCLUSIONS: CSF-based liquid biopsy showed potential feasibility for molecular analysis of primary intramedullary astrocytoma through sequencing of ctDNA. This approach may assist in diagnosis and prognostic evaluation of this rare spinal cord tumor.
摘要：
目的：尽管基于脑脊液（CSF）的液体活检被证明在颅内胶质瘤的分子分析中是可行的，原发性髓内星形细胞瘤的液体活检很少报道。鉴于原发性髓内神经胶质瘤和颅内星形细胞瘤之间不同的基因组谱，是否可以在原发性脊髓星形细胞瘤中复制基于CSF的颅内神经胶质瘤分子分析的可行性尚需研究.这项初步研究的目的是通过对CSF衍生的循环肿瘤DNA（ctDNA）进行测序来评估原发性髓内星形细胞瘤分子分析的可行性。
方法：两个IV级弥漫性中线胶质瘤，一级二级,包括1级星形细胞瘤。术中采集外周血和脑脊液样本，以及术后收集匹配的肿瘤组织。一个涵盖1,021个最常见的实体瘤驱动基因的小组用于靶向DNA测序。
结果：在3个CSF样本（2个IV级弥漫性中线神经胶质瘤和1个I级星形细胞瘤）中检测到CSF来源的ctDNA，在肿瘤组织和CSF样本中均发现5个突变，而仅在肿瘤组织和CSF样本中检测到11个突变和20个突变，分别。重要的是,热点遗传改变，包括H3F3AK28M，TP53和ATRX，在CSF中鉴定，CSF中的平均突变等位基因频率通常高于肿瘤组织。
结论：基于CSF的液体活检显示通过ctDNA测序对原发性髓内星形细胞瘤进行分子分析的潜在可行性。这种方法可能有助于这种罕见的脊髓肿瘤的诊断和预后评估。
方法：两个IV级弥漫性中线胶质瘤，一级二级,包括1级星形细胞瘤。术中采集外周血和脑脊液样本，以及术后收集匹配的肿瘤组织。一个涵盖1,021个最常见的实体瘤驱动基因的小组用于靶向DNA测序。
结果：在3个CSF样本（2个IV级弥漫性中线神经胶质瘤和1个I级星形细胞瘤）中检测到CSF来源的ctDNA，在肿瘤组织和CSF样本中均发现5个突变，而仅在肿瘤组织和CSF样本中检测到11个突变和20个突变，分别。重要的是,热点遗传改变，包括H3F3AK28M，TP53和ATRX，在CSF中鉴定，CSF中的平均突变等位基因频率通常高于肿瘤组织。
结论：基于CSF的液体活检显示通过ctDNA测序对原发性髓内星形细胞瘤进行分子分析的潜在可行性。这种方法可能有助于这种罕见的脊髓肿瘤的诊断和预后评估。
