Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases.
Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases.
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DOI：
10.1007/s11060-016-2081-5
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发表时间：
2016-05
影响因子：
3.9
通讯作者：
Gephart MH
中科院分区：
文献类型：
--
作者：
Li Y;Pan W;Connolly ID;Reddy S;Nagpal S;Quake S;Gephart MH
来自脑肿瘤患者的脑脊液（CSF）含有肿瘤细胞和无细胞DNA（cfDNA），其提供了一种侵入性较小且常规可获得的方法来获得肿瘤基因组信息。在这份报告中，我们使用液滴数字PCR检测患者CSF中的突变肿瘤DNA，以监测转移性黑色素瘤软脑膜疾病（LMD）的治疗反应。已知原发性黑色素瘤有BRAFV600E突变，患者接受全脑放疗和BRAF抑制剂治疗。我们在6个月内收集了9份CSF样本。在前6个时间点，突变cfDNA分数从53%（诊断时间）逐渐降低至0（症状缓解时间）。在临床改善后三个月，患者返回，症状严重，并且在CSF中再次检测到高水平的突变cfDNA。突变体DNA分数与患者的临床反应一致。我们使用全外显子组测序来检查治疗反应前和疾病复发后CSF中LMD肿瘤DNA的突变谱，并在两个时间点发现了典型的癌症突变PTENR 130 *。细胞和cfDNA显示出相似的突变谱，表明cfDNA代表LMD细胞。本研究证明了使用CSF中的细胞或cfDNA监测LMD的治疗反应的潜力。
Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAFV600E mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient’s clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTENR130* at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD.