Brain tumor mutations detected in cerebral spinal fluid.
Brain tumor mutations detected in cerebral spinal fluid.
复制标题
DOI：
10.1373/clinchem.2014.235457
复制
发表时间：
2015-03
影响因子：
9.3
通讯作者：
Quake SR
中科院分区：
文献类型：
--
作者：
Pan W;Gu W;Nagpal S;Gephart MH;Quake SR
在脑肿瘤患者的血液中检测肿瘤来源的无细胞DNA（cfDNA）是具有挑战性的，可能是由于血脑屏障。脑脊髓液（CSF）可作为脑肿瘤的替代“液体活检”，通过测量CSF中的循环DNA来表征肿瘤特异性突变。关于CSF中肿瘤突变的特征和可检测性的许多方面仍未确定。我们使用数字PCR和靶向扩增子测序来定量从7名患有实体脑肿瘤的患者收集的CSF和血浆的cfDNA中的肿瘤突变。此外，我们应用癌症组测序对1例疑似软脑膜疾病患者CSF的体细胞突变谱进行了全面表征。我们在7例实体性脑肿瘤患者中的6例的CSF样本中检测到肿瘤突变。肿瘤突变等位基因的浓度在患者之间变化很大，从<5到接近3000拷贝/mL CSF。我们通过使用癌症组测序从患有软脑膜疾病的患者的CSF中鉴定出7个体细胞突变，并且结果与原发性肿瘤活检的基因检测一致。在来自患有不同原发性和转移性脑肿瘤的患者的CSF的cfDNA中可检测到肿瘤突变。我们设计了2种策略来表征CSF中的肿瘤突变以用于潜在的临床诊断：靶向检测已知的驱动突变以监测脑转移，以及基因组畸变的全局表征以指导个性化癌症护理。
Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain tumor patients is challenging, presumably owing to the blood–brain barrier. Cerebral spinal fluid (CSF) may serve as an alternative “liquid biopsy” of brain tumors by enabling measurement of circulating DNA within CSF to characterize tumor-specific mutations. Many aspects about the characteristics and detectability of tumor mutations in CSF remain undetermined. We used digital PCR and targeted amplicon sequencing to quantify tumor mutations in the cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also, we applied cancer panel sequencing to globally characterize the somatic mutation profile from the CSF of 1 patient with suspected leptomeningeal disease. We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain tumors. The concentration of the tumor mutant alleles varied widely between patients, from <5 to nearly 3000 copies/mL CSF. We identified 7 somatic mutations from the CSF of a patient with leptomeningeal disease by use of cancer panel sequencing, and the result was concordant with genetic testing on the primary tumor biopsy. Tumor mutations were detectable in cfDNA from the CSF of patients with different primary and metastatic brain tumors. We designed 2 strategies to characterize tumor mutations in CSF for potential clinical diagnosis: the targeted detection of known driver mutations to monitor brain metastasis and the global characterization of genomic aberrations to direct personalized cancer care.