Review: Peering through a keyhole: liquid biopsy in primary and metastatic central nervous system tumours

Abstract

2019) Neuropathology and Applied Neurobiology 45, 655-670 Peering through a keyhole: liquid biopsy in primary and metastatic central nervous system tumours Tumour molecular profiling by liquid biopsy is being investigated for a wide range of research and clinical purposes. The possibility of repeatedly interrogating the tumour profile using minimally invasive procedures is helping to understand spatial and temporal tumour heterogeneity, and to shed a light on mechanisms of resistance to targeted therapies. Moreover, this approach has been already implemented in clinical practice to address specific decisions regarding patients' follow-up and therapeutic management. For central nervous system (CNS) tumours, molecular profiling is particularly relevant for the proper characterization of primary neoplasms, while CNS metastases can significantly diverge from primary disease or extra-CNS metastases, thus compelling a dedicated assessment. Based on these considerations, effective liquid biopsy tools for CNS tumours are highly warranted and a significant amount of data have been accrued over the last few years. These results have shown that liquid biopsy can provide clinically meaningful information about both primary and metastatic CNS tumours, but specific considerations must be taken into account, for example, when choosing the source of liquid biopsy. Nevertheless, this approach is especially attractive for CNS tumours, as repeated tumour sampling is not feasible. The aim of our review was to thoroughly report the state-of-the-art regarding the opportunities and challenges posed by liquid biopsy in both primary and secondary CNS tumours.

ctDNA as a Cancer Biomarker: A Broad Overview

“…The low sensitivity of liquid plasma biopsy for the diagnosis of CNS tumors has been suggested by the presence of the blood brain barrier (BBB), which hinders the circulation of tumor components in the blood. Therefore, the vast majority of liquid biopsy studies in these cases use cerebrospinal fluid as an alternative diagnostic sample, aiming at its direct contact with the CNS (Bertero et al, 2019). The feasibility of detecting ctDNA in patients with secondary CNS tumor involvement has been demonstrated in studies of breast carcinoma, melanoma and secondary hematologic malignancies (Li et al, 2016).…”

“…In addition to the cerebrospinal liquid already mentioned, analysis of circulating platelets seems to be another intriguing approach to achieve liquid biopsy of CNS tumors. Many biomolecules are transferred between tumors and platelets, and this process has been termed platelet "education" (Bertero et al, 2019;Best et al, 2018). Platelets can sequester tumor-shed extracellular vesicles, which allow the detection of tumor-derived biomarkers, including proteins and nucleic acids, with high sensitivity and specificity (Klement et al, 2009;Kuznetsov et al, 2012).…”

“…Platelets can sequester tumor-shed extracellular vesicles, which allow the detection of tumor-derived biomarkers, including proteins and nucleic acids, with high sensitivity and specificity (Klement et al, 2009;Kuznetsov et al, 2012). In 114 samples (62 patients) with brain lesions, tumor-educated platelet analysis allowed assertive identification of cancer in 91% of patients and discernment between the mutational subtypes in 82% of cases (Bertero et al, 2019;Best et al, 2018).…”

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis

“…Lastly, considering the growing importance of extensive molecular profiling to tailor patients' treatments, liquid biopsy approaches could be applied to overcome the limitations in sampling CNS lesions. Although the analysis of circulating tumor DNA (ctDNA) or of other nucleic acids it is not commonly used in clinical practice for sampling BMs from OC, multiple reports [83,84] showed the possibility to gather informative data in multiple types of primary and secondary CNS tumors; thus, this possibility could be investigated in future studies targeting OC BMs.…”

Detection of IDH mutations in cerebrospinal fluid: A discussion of liquid biopsy in neuropathology

“…Before the introduction of techniques like digital polymerase chain reaction (PCR) [34] beads, emulsion, ampli ication, and magnetics (BEAMing) [34]. detection of cfDNA derived from tumours was inconsistently detected [33], with some authors suggesting that ctDNA was inferior to other circulating biomarkers [32,35,36].…”