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

McEwen, Abbye E.; Leary, Sarah E. S.; Lockwood, Christina M.

doi:10.3389/fcell.2020.00045

Cited by 54 publications

(50 citation statements)

References 84 publications

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“…Furthermore, highly sensitive methods such as WGS and NGS require additional technical and bioinformatic approaches to facilitate enhanced the ability to detect tumour mutations in CSF cfDNA. Hence, they can be costly and time-consuming [ 52 ]. Although there is an alternative option of using droplet digital PCR, users require prior knowledge of the specific mutations they want to test for, and the technology may be only limited up to 4 targets per assay [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore

Low

Zou

et al. 2020

BMC Neurol

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Background Germinomas (IG) account for up to 50% of all intracranial germ cell tumours. These tumours are reputed to be more prevalent in Oriental populations in comparison to Western cohorts. Biological characteristics of IG in other ethnic groups are unknown. Singapore is a multi-ethnic country with diverse cultures. Owing to inter-racial heterogeneity, the authors hypothesize there are molecular differences between paediatric IG patients in our local population. The aims of this study are exploratory: firstly, to identify molecular characteristics in this tumour type and circulating CSF unique to different racial cohorts; and next, to corroborate our findings with published literature. Methods This is a single-institution, retrospective study of prospectively collected data. Inclusion criteria encompass all paediatric patients with histologically confirmed IG. Excess CSF and brain tumour tissues are collected for molecular analysis. Tumour tissues are subjected to a next generation sequencing (NGS) targeted panel for KIT and PDGRA. All CSF samples are profiled via a high-throughput miRNA multiplexed workflow. Results are then corroborated with existing literature and public databases. Results In our cohort of 14 patients, there are KIT exon variants in the tumour tissues and CSF miRNAs corroborative with published studies. Separately, there are also KIT exon variants and miRNAs not previously highlighted in IG. A subgroup analysis demonstrates differential CSF miRNAs between Chinese and Malay IG patients. Conclusion This is the first in-depth molecular study of a mixed ethnic population of paediatric IGs from a Southeast Asian cohort. Validation studies are required to assess the relevance of novel findings in our study.

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Section: Discussionmentioning

confidence: 99%

Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore

Low

Zou

et al. 2020

BMC Neurol

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“…This means that processing a small biopsy might not represent the whole tumor. Likewise, molecular testing of a primary extracranial cancer could be insufficient to guide treatment decisions for its CNS metastasis [ 9 , 63 , 66 , 67 ].…”

Section: Cns Cancersmentioning

confidence: 99%

“…Liquid molecular analysis could facilitate tumor diagnosis, monitoring, and therapy selection, and overcome inherent problems related to a tissue biopsy. Similar to tissues, cancer mutational testing can be performed in body fluids such as the blood, urine, sputum, pleural fluid, and CSF [ 9 , 68 – 70 ]. Even if it often fails to reach the diagnostic capacity of its tissue counterpart and lacks sufficient evidence of clinical validity and utility, the liquid biopsy is minimally invasive, cheaper than tissue biopsy, easier to obtain, and free from preservatives and fixatives.…”

Section: Cns Cancersmentioning

confidence: 99%

“…While the presence of oligoclonal bands—which represent increased concentrations of IgG immunoglobulins—in the CSF characterizes most MS cases, these bands could also be detected in other inflammatory or even neoplastic CNS conditions [ 8 ]. Of interest, CSF examination could provide answers where other diagnostic modalities fail or may harm the patients; for instance, when a brain biopsy fails to diagnose and assess the molecular profile of a CNS tumor or it is contraindicated due to the tumor location or the condition of the patient’s health, CSF testing is a viable option [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluating Infectious, Neoplastic, Immunological, and Degenerative Diseases of the Central Nervous System with Cerebrospinal Fluid-Based Next-Generation Sequencing

et al. 2021

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Cerebrospinal fluid (CSF) is a clear and paucicellular fluid that circulates within the ventricular system and the subarachnoid space of the central nervous system (CNS), and diverse CNS disorders can impact its composition, volume, and flow. As conventional CSF testing suffers from suboptimal sensitivity, this review aimed to evaluate the role of next-generation sequencing (NGS) in the work-up of infectious, neoplastic, neuroimmunological, and neurodegenerative CNS diseases. Metagenomic NGS showed improved sensitivity—compared to traditional methods—to detect bacterial, viral, parasitic, and fungal infections, while the overall performance was maximized in some studies when all diagnostic modalities were used. In patients with primary CNS cancer, NGS findings in the CSF were largely concordant with the molecular signatures derived from tissue-based molecular analysis; of interest, additional mutations were identified in the CSF in some glioma studies, reflecting intratumoral heterogeneity. In patients with metastasis to the CNS, NGS facilitated diagnosis, prognosis, therapeutic management, and monitoring, exhibiting higher sensitivity than neuroimaging, cytology, and plasma-based molecular analysis. Although evidence is still rudimentary, NGS could enhance the diagnosis and pathogenetic understanding of multiple sclerosis in addition to Alzheimer and Parkinson disease. To conclude, NGS has shown potential to aid the research, facilitate the diagnostic approach, and improve the management outcomes of all the aforementioned CNS diseases. However, to establish its role in clinical practice, the clinical validity and utility of each NGS protocol should be determined. Lastly, as most evidence has been derived from small and retrospective studies, results from randomized control trials could be of significant value.

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“…Cerebrospinal fluid (CSF) could represent the best approach for minimally invasive diagnostics and disease monitoring of central nervous system (CNS) malignancies [ 178 ] in which plasma ctDNA is very low or absent [ 16 ]. In comparison with blood, the analysis of ctDNA in CSF has several advantages, including the following: lack of non-tumor cell-free DNA due to paucicellular nature of CSF; enriched ctDNA in CSF of patients with CNS-limited tumors; the fact that mutations in CSF ctDNA are most concordant with intracranial processes in metastatic CNS cancer; and the fac that CSF ctDNA could also uncover additional genetic aberrations reflecting tumor heterogeneity [ 179 ]. Importantly, CSF-based liquid biopsy has been demonstrated to be more sensitive than plasma-based in the management of patients with ALK (anaplastic lymphoma kinase)-rearranged NSCLC with leptomeningeal metastases [ 76 ].…”

Section: Other Liquid Biopsy Typesmentioning

confidence: 99%

Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management

Líšková

Samec

Koklesová

et al. 2020

JCM

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One in every four deaths is due to cancer in Europe. In view of its increasing incidence, cancer became the leading cause of death and disease burden in Denmark, France, the Netherlands, and the UK. Without essential improvements in cancer prevention, an additional 775,000 cases of annual incidence have been prognosed until 2040. Between 1995 and 2018, the direct costs of cancer doubled from EUR 52 billion to EUR 103 billion in Europe, and per capita health spending on cancer increased by 86% from EUR 105 to EUR 195 in general, whereby Austria, Germany, Switzerland, Benelux, and France spend the most on cancer care compared to other European countries. In view of the consequent severe socio-economic burden on society, the paradigm change from a reactive to a predictive, preventive, and personalized medical approach in the overall cancer management is essential. Concepts of predictive, preventive, and personalized medicine (3PM) demonstrate a great potential to revise the above presented trends and to implement cost-effective healthcare that benefits the patient and society as a whole. At any stage, application of early and predictive diagnostics, targeted prevention, and personalization of medical services are basic pillars making 3PM particularly attractive for the patients as well as ethical and cost-effective healthcare. Optimal 3PM approach requires novel instruments such as well-designed liquid biopsy application. This review article highlights current achievements and details liquid biopsy approaches specifically in cancer management. 3PM-relevant expert recommendations are provided.

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

Cited by 54 publications

References 84 publications

Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore

Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore

Evaluating Infectious, Neoplastic, Immunological, and Degenerative Diseases of the Central Nervous System with Cerebrospinal Fluid-Based Next-Generation Sequencing

Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management

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