Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA

Pan, Changcun; Diplas, Bill H.; Chen, Xin; Wu, Yadong; Xiao, Xiong; Jiang, Liping; Geng, Yibo; Xu, Changwu; Sun, Yu; Zhang, Peng; Wu, Wenhao; Wang, Yu; Wu, Zhen; Zhang, Junting; Jiao, Yuchen; Yan, Hai; Zhang, Liwei

doi:10.1007/s00401-018-1936-6

Cited by 114 publications

(125 citation statements)

References 40 publications

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“…In a study of 57 patients, a next-generation sequencing (NGS) panel of 68 genes commonly mutated in brain stem tumors detected tumor specific mutations in the CSF cfDNA of 82.5% of patients. Consistent with molecular findings from tumor-based studies, two markers in this panel were shown to correlate with overall survival (OS) in patients with diffuse midline glioma in this cohort -the presence of an H3F3A/HIST1H3B mutation was predictive of poor overall survival consistent with the specific entity of H3K27M-mutant diffuse midline glioma, where as an IDH1 mutation predicted better OS (Pan et al, 2019). Targeted therapies for these alterations are currently undergoing clinical trials (Long et al, 2017).…”

Section: Brainstem Tumorssupporting

confidence: 76%

“…Physiologic factors include those that limit the amount of tumorderived cfDNA present in the CSF. Multiple studies have shown that low grade tumors or those not directly communicating with the CSF space have low to undetectable tumor-derived cfDNA in the CSF Juratli et al, 2018;Martínez-Ricarte et al, 2018;Pan et al, 2019). Likewise, detection of tumor-derived cfDNA is less likely in patients with new onset disease (Pan et al, 2019).…”

Section: Preanalytical Variablesmentioning

confidence: 99%

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Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

McEwen

Leary

Lockwood

2020

Front. Cell Dev. Biol.

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Section: Brainstem Tumorssupporting

confidence: 76%

Section: Preanalytical Variablesmentioning

confidence: 99%

Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

McEwen

Leary

Lockwood

2020

Front. Cell Dev. Biol.

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“…Detection of CSF ctDNA is convenient, comprehensive, and less invasive for the diagnosis of brain lesions and may offer an alternative method to stereotactic biopsy. 9 The importance of CSF in guiding the treatment of cancerous brain lesions has been verified in some small-sample studies showing that it could relatively accurately represent the genomic mutation of brain tumors. [10][11][12][13][14] Nevertheless, data on brain metastases are still very limited.…”

Section: Introductionmentioning

confidence: 99%

“…Tumor load can be evaluated using imaging, such as magnetic resonance imaging (MRI), but CSF liquid biopsy could facilitate dynamic monitoring of the therapeutic effect on brain lesions, indicating the prognosis. Detection of CSF ctDNA is convenient, comprehensive, and less invasive for the diagnosis of brain lesions and may offer an alternative method to stereotactic biopsy …”

Section: Introductionmentioning

confidence: 99%

“…A study by Pan et al 9 demonstrated that sequencing of CSF ctDNA in patients with brainstem glioma could characterize molecular alterations of the tumor more comprehensively than tissue biopsy from a single site, and the results were superior to those of blood ctDNA. The genomic and molecular characteristics of brain lesions change with treatment and treatment line progression.…”

Section: Introductionmentioning

confidence: 99%

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Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

Yang

Xing

et al. 2020

Thoracic Cancer

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Background Evaluating the molecular characteristics of brain metastases is limited by difficult access and by the blood–brain barrier, which prevents circulating tumor DNA (ctDNA) from entering the blood. In this study, we aimed to compare the sequencing results from cerebrospinal fluid (CSF) ctDNA versus plasma ctDNA, plasma circulating tumor cells (CTCs), and brain tissue specimens from patients with brain metastasis from non‐small cell lung cancer (NSCLC). Methods This was a prospective study of 21 consecutive patients with NSCLC and brain metastasis diagnosed between April 2018 and January 2019. Samples of CSF and peripheral blood were obtained from all 21 patients. Brain tissues were obtained from five patients after surgical resection. Next‐generation sequencing was performed using the Ion system. Single nucleotide variants (SNVs) and small insertions or deletions (indels) were searched. Results Mutations were detected in the CSF ctDNA of 20 (95.2%) patients. The detection rate of epidermal growth factor receptor (EGFR) mutations in CSF ctDNA was 57.1% (12/21) whereas this rate was only 23.8% (5/21) in peripheral blood ctDNA and in CTCs. EGFR mutations were found in the CSF of 9 of 11 (81.8%) patients with leptomeningeal metastases, as compared with three of 10 (30%) patients with brain parenchymal metastases. Mutations were also detected in KIT, PIK3CA, TP53, SMAD4, ATM, SMARCB1, PTEN, FLT3, GNAS, STK11, MET, CTNNB1, APC, FBXW7, ERBB4, and KDR (all >10%). The status of EGFR and TP53 mutations was consistent between CSF ctDNA and brain lesion tissue in all five patients. Conclusion Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastasis. Key points In some small‐sample studies, the importance of cerebrospinal fluid in guiding the treatment of cancerous brain lesions has been verified in that it may reflect genomic mutations of brain tumors relatively accurately. Cerebrospinal fluid is a new form of liquid biopsy that can be helpful in improving the management of patients with brain metastasis from non‐small cell lung cancer by detecting genetic abnormalities specific to brain metastases.

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Clinicopathological characteristics and survival of spinal cord astrocytomas

et al. 2020

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Molecular profiling of tumors of the brainstem by sequencing of CSF-derived circulating tumor DNA

Cited by 114 publications

References 40 publications

Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

Clinicopathological characteristics and survival of spinal cord astrocytomas

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