Neurology Unit, IRCCS Ospedale San Raffaele.
Vita-Salute San Raffaele University.
Curr Opin Oncol. 2024 Nov 1;36(6):521-529. doi: 10.1097/CCO.0000000000001079. Epub 2024 Jul 10.
Due to limited access to the tumor, there is an obvious clinical potential for liquid biopsy in patients with primary brain tumors. Here, we review current approaches, present limitations to be dealt with, and new promising data that may impact the field.
The value of circulating tumor cell-free DNA (ctDNA) in the cerebrospinal fluid (CSF) for the noninvasive diagnosis of primary brain tumors has been confirmed in several reports. The detection of ctDNA in the peripheral blood is desirable for patient follow-up but requires ultrasensitive methods to identify low mutant allelic frequencies. Digital PCR approaches and targeted gene panels have been used to identify recurrent hotspot mutations and copy number variations (CNVs) from CSF or plasma. Tumor classification from circulating methylomes in plasma has been actively pursued, although the need of advanced bioinformatics currently hampers clinical application. The use of focused ultrasounds to open the blood-brain barrier may represent a way to enrich of ctDNA the peripheral blood and enhance plasma-based liquid biopsy.
Monitoring CNVs and hotspot mutations by liquid biopsy is a promising tool to detect minimal residual disease and strengthen response assessment in patients with primary brain tumors. Novel methods to increase the relative and/or absolute amount of ctDNA can improve the clinical potential of plasma-based liquid biopsies.
由于肿瘤的获取有限，液体活检在原发性脑肿瘤患者中具有明显的临床应用潜力。本文回顾了当前的方法、需要解决的局限性以及可能影响该领域的新的有前途的数据。
已有多项报道证实，脑脊液（CSF）中循环肿瘤细胞游离 DNA（ctDNA）对原发性脑肿瘤的无创诊断具有价值。外周血中 ctDNA 的检测对患者的随访很有意义，但需要超灵敏的方法来识别低突变等位基因频率。数字 PCR 方法和靶向基因 panel 已被用于从 CSF 或血浆中识别复发的热点突变和拷贝数变异（CNV）。从血浆中的循环甲基组学进行肿瘤分类得到了积极的研究，尽管目前先进的生物信息学的需求阻碍了临床应用。使用聚焦超声打开血脑屏障可能是一种富集外周血 ctDNA 并增强基于血浆的液体活检的方法。
通过液体活检监测 CNV 和热点突变是一种很有前途的工具，可以检测原发性脑肿瘤患者的微小残留疾病并加强对其的反应评估。增加 ctDNA 的相对和/或绝对量的新方法可以提高基于血浆的液体活检的临床应用潜力。
