Zhu Zhongyuan, Yu Yanjiao, Liu Fuzhong, Yang Xiaosong, Zhou Zijie, Zhu Zhengquan, Wang Zifeng, Zhang Ji
Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
J Mol Neurosci. 2025 Jun 20;75(3):79. doi: 10.1007/s12031-025-02361-4.
Diffuse gliomas are aggressive brain tumors known for heterogeneity and frequent oncogenic mutations. Our study harnessed circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) as a less invasive method for disease monitoring and guiding therapeutic interventions. Through targeted sequencing of ctDNA from CSF and matched blood and tumor tissue samples, we aimed to identify glioma-associated somatic alterations and DNA fragmentations. The identified glioma-associated mutations from ctDNA in CSF and genome DNA of the resected tumor were compared, revealed a broad genetic alteration spectrum within CSF ctDNA, closely reflecting the genomic profiles of corresponding tumor samples. And we found 91.67% (11/12) of tissue samples analyzed by next-generation sequencing (NGS), a minimum of one tumor-specific mutation was present. Also, at least one tumor-specific mutation was detected in 91.67% of serial CSF ctDNA samples (11/12). In some patients, CSF sequencing showed higher mutation detection rate compared to tissue sequencing. Moreover, the average mutation frequencies were similar between CSF and tumor tissue samples. These results support that CSF ctDNA is a reliable candidate for detecting glioma-specific alterations for molecular profiling, complements the histopathological, molecular and imaging defect, and can be adopted into clinical practice.
弥漫性胶质瘤是一种侵袭性脑肿瘤，以异质性和频繁的致癌突变为特征。我们的研究利用脑脊液（CSF）中的循环肿瘤DNA（ctDNA）作为一种侵入性较小的疾病监测和指导治疗干预的方法。通过对来自脑脊液、匹配血液和肿瘤组织样本的ctDNA进行靶向测序，我们旨在识别胶质瘤相关的体细胞改变和DNA片段化。对脑脊液中ctDNA和切除肿瘤的基因组DNA中鉴定出的胶质瘤相关突变进行比较，发现脑脊液ctDNA中存在广泛的基因改变谱，密切反映了相应肿瘤样本的基因组概况。我们发现，通过下一代测序（NGS）分析的组织样本中有91.67%（11/12）至少存在一个肿瘤特异性突变。此外，在91.67%的连续脑脊液ctDNA样本（11/12）中也检测到至少一个肿瘤特异性突变。在一些患者中，脑脊液测序显示出比组织测序更高的突变检测率。此外，脑脊液和肿瘤组织样本之间的平均突变频率相似。这些结果支持脑脊液ctDNA是检测胶质瘤特异性改变以进行分子谱分析的可靠候选者，可补充组织病理学、分子和影像学缺陷，并可应用于临床实践。
