Gavrjushin A V, Papusha L I, Veselkov A A, Zaitseva M A, Khukhlaeva E A, Konovalov A N, Druy A E
Burdenko Neurosurgical Center, Moscow, Russia.
National Medical Research Center for Pediatric Hematology, Oncology and Immunology Named After Dmitry Rogachev, Moscow, Russia.
Neurosurg Rev. 2025 May 26;48(1):442. doi: 10.1007/s10143-025-03593-z.
The treatment of diffuse brainstem tumors is prescribed in most cases without morphological or molecular genetic verification. "Liquid biopsy" is a minimally invasive technique that provides information about the biology of tumors without a standard biopsy. We set out to determine the informativeness of this diagnostic method for detecting H3K27 and BRAF V600E mutations in patients with diffuse brainstem tumors. Thirty patients (10 children, 20 adults) with radiologically verified brainstem tumors underwent CSF collection via lumbar puncture. Cell-free DNA (cfDNA) isolated from the CSF was used for detection of H3F3A K28M and BRAF V600E mutations via digital droplet PCR. In 23 patients, the study of these mutations was performed in parallel in the pool of cfDNA and DNA isolated from tumor tissue obtained during a standard tumor biopsy. A mutation in the BRAF gene was not detected in any patient. The H3F3A K28M mutation was detected in 7 samples of cfDNA and 8 samples of DNA isolated from tumor tissue obtained from 23 patients for whom the study was performed in parallel. The sensitivity and specificity of H3F3A K28M mutation detection in CSF and tumor tissue were 87.5% and 100%, respectively (P < 0.001, relative risk = 0.063, 95% CI: 0.009-0.417). Minimally invasive diagnosis of diffuse brainstem tumors via the "liquid biopsy" method is informative for the detection of specific H3F3A K28M mutations and allows the verification of the diagnosis of diffuse midline glioma with H3K27 (H3K28M) alterations without a standard biopsy. Despite the promising results, an important limitation of the work is the small sample size, which affects the statistical results and conclusions. Large multicenter studies are needed to further investigate the value of liquid biopsy in brainstem gliomas.
在大多数情况下，弥漫性脑干肿瘤的治疗方案是在未进行形态学或分子遗传学验证的情况下制定的。“液体活检”是一种微创技术，无需进行标准活检即可提供有关肿瘤生物学特性的信息。我们旨在确定这种诊断方法对检测弥漫性脑干肿瘤患者中H3K27和BRAF V600E突变的信息量。30例经放射学证实患有脑干肿瘤的患者（10名儿童，20名成人）通过腰椎穿刺收集脑脊液。从脑脊液中分离出的游离DNA（cfDNA）用于通过数字液滴PCR检测H3F3A K28M和BRAF V600E突变。在23例患者中，对这些突变的研究在cfDNA样本和从标准肿瘤活检获得的肿瘤组织中分离出的DNA样本中同时进行。在任何患者中均未检测到BRAF基因的突变。在23例同时进行研究的患者中，从肿瘤组织中分离出的cfDNA样本中有7例以及DNA样本中有8例检测到H3F3A K28M突变。脑脊液和肿瘤组织中H3F3A K28M突变检测的敏感性和特异性分别为87.5%和100%（P < 0.001，相对风险=0.063，95%置信区间：0.009 - 0.417）。通过“液体活检”方法对弥漫性脑干肿瘤进行微创诊断对于检测特定的H3F3A K28M突变具有信息量，并且无需进行标准活检即可验证弥漫性中线胶质瘤伴H3K27（H3K28M）改变的诊断。尽管取得了有前景的结果，但该研究的一个重要局限性是样本量小，这影响了统计结果和结论。需要进行大型多中心研究以进一步探讨液体活检在脑干胶质瘤中的价值。
