A feasibility study of enzymatic methylation sequencing of cell-free DNA from cerebrospinal fluid of pediatric central nervous system tumor patients for molecular classification.

Background: Array-based DNA methylation profiling is the gold standard for central nervous system (CNS) tumor molecular classification, but requires over 100 ng input DNA from surgical tissue. Cell-free tumor DNA (cfDNA) in cerebrospinal fluid (CSF) offers an alternative for diagnosis and disease monitoring. This study aimed to test the utilization of enzymatic DNA methylation sequencing (EM-seq) methods to overcome input DNA limitations.

Advancing sarcoma diagnostics with expanded DNA methylation-based classification.

Purpose: Sarcomas pose a severe diagnostic challenge. A wide variety of these distinct entities need to be distinguished from each other and from less aggressive types of mesenchymal tumors, to ensure correct clinical management. A machine learning based classifier for sarcomas utilizing DNA methylation data from 1077 tumors recognizing 62 sarcoma types has already been developed and termed the sarcoma classifier, which we published in 2021.

Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.

DNA methylation-based classification is integral to contemporary neuro-oncological diagnostics, as highlighted by the current World Health Organization (WHO) classification of central nervous system (CNS) tumors. We introduce the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.

ROBIN: A unified nanopore-based assay integrating intraoperative methylome classification and next-day comprehensive profiling for ultra-rapid tumor diagnosis.

Background: Advances in our technological capacity to interrogate CNS tumor biology have led to the ever increasing use of genomic sequencing in diagnostic decision making. Presently, CNS tumors are classified based on their epigenetic signatures, leading to a paradigm shift in diagnostic pathways. Such testing can be performed so rapidly using nanopore sequencing that results can be provided intraoperatively.

Prospective, multicenter validation of a platform for rapid molecular profiling of central nervous system tumors.

Molecular data integration plays a central role in central nervous system (CNS) tumor diagnostics but currently used assays pose limitations due to technical complexity, equipment and reagent costs, as well as lengthy turnaround times. We previously reported the development of Rapid-CNS, an adaptive-sampling-based nanopore sequencing workflow. Here we comprehensively validated and further developed Rapid-CNS for intraoperative use.

Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics.

The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility.

Accurate and comprehensive evaluation of O6-methylguanine-DNA methyltransferase promoter methylation by nanopore sequencing.

Aims: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter region is essential in evaluating the prognosis and predicting the drug response in patients with glioblastoma. In this study, we evaluated the utility of using nanopore long-read sequencing as a method for assessing methylation levels throughout the MGMT CpG-island, compared its performance to established techniques and demonstrated its clinical applicability.

Methods: We analysed 165 samples from CNS tumours, focusing on the MGMT CpG-island using nanopore sequencing.

Cerebrospinal Fluid cfDNA Sequencing for Classification of Central Nervous System Glioma.

Purpose: Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.

Experimental Design: We performed targeted next-generation sequencing of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma.

Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma.

An obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors.

Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

Purpose: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance.

Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds.

Phytomedicine has often been used as "alternative therapy," which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply "working" through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds. Although fluctuation in efficacy due to seasonal and geographical variations in phytomedicine remains a concern, if well regulated, even plant extracts without isolated compounds can serve medicinal needs where single-compound options are currently not great.