A5025533141- Glioma Diagnosis and Treatment
- Meningioma and schwannoma management
- Cancer Genomics and Diagnostics
- Brain Metastases and Treatment
- Pituitary Gland Disorders and Treatments
- Head and Neck Surgical Oncology
- Brain Tumor Detection and Classification
- Bone Tumor Diagnosis and Treatments
- Single-cell and spatial transcriptomics
- Radiomics and Machine Learning in Medical Imaging
- Extracellular vesicles in disease
- Chromatin Remodeling and Cancer
- Neuroendocrine Tumor Research Advances
- ATP Synthase and ATPases Research
- Computational Drug Discovery Methods
- Lung Cancer Treatments and Mutations
- Neurofibromatosis and Schwannoma Cases
- Shoulder and Clavicle Injuries
- Ocular Oncology and Treatments
- Advanced Electron Microscopy Techniques and Applications
- Neurogenesis and neuroplasticity mechanisms
- Myasthenia Gravis and Thymoma
- Epigenetics and DNA Methylation
- Nanopore and Nanochannel Transport Studies
- Gestational Trophoblastic Disease Studies
University Hospital Heidelberg
2021-2024
Heidelberg University
2020-2024
German Cancer Research Center
2020-2024
Heidelberg (Poland)
2023
University of Toronto
2023
Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk progression for individual patients is pivotal importance. However, only biomarkers aggressive tumors established (CDKN2A/B and TERT), whereas no molecularly based stratification exists broad spectrum with low- intermediate-risk meningioma.DNA methylation data copy-number information were generated 3,031...
Abstract Both the perivascular niche (PVN) and integration into multicellular networks by tumor microtubes (TMs) have been associated with progression resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of cell fate dynamics live mouse brain, differential therapeutic responses both niches are determined. PVN, a preferential location quiescent glioma cells, network facilitate against cytotoxic effects radiotherapy...
Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data 1577 meningioma samples from 6 independent cohorts enriched clinically aggressive meningiomas comprehensively interrogate spectrum...
Abstract Clear cell meningioma represents an uncommon variant of that typically affects children and young adults. Although enrichment loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset tumors ( n = 31), initially identified through genome-wide DNA methylation screening among cohort 3093 meningiomas, which most were diagnosed histologically as clear meningioma....
Abstract The 2021 WHO classification underscores the importance of molecular data integration in Central Nervous System (CNS) tumor diagnostics. However, currently used assays have disadvantages due to technical complexity, required equipment and reagent cost, as well lengthy turnaround times. In response these challenges, we introduce Rapid-CNS 2 MNP-Flex. , an adaptive sampling-based nanopore sequencing workflow, offers real-time methylation DNA copy-number information within a 30-minute...
ABSTRACT Meningiomas are the most frequent primary intracranial tumors. They can follow a wide clinical spectrum from benign to highly aggressive course. No specific therapy exists for refractory cases or not amenable resection and radiotherapy. Identification of risk recurrence malignant transformation individual patients is challenging. However, promising molecular markers prognostic subgrouping by DNA methylation emerging. Still, biological underpinnings these diagnostic subgroups...
Abstract BACKGROUND The 2021 WHO classification update highlights the necessity of integrating molecular alterations for precise central nervous system (CNS) tumor diagnoses. However, current reporting methods are hindered by significant initial investment, labor-intensive protocols, and lengthy turnaround times. Methylation-based has emerged as a pivotal diagnostic tool but is currently limited to array-based techniques. This necessitates exploration novel technologies streamline analysis....
Abstract The WHO classification of CNS tumours 2021 recommends reporting a wide range molecular alterations for WHO-compatible diagnoses. Conventional workflows warrant considerable investment and long turnaround times limited by batching. Nanopore sequencing enables read sequencing, real-time targeting simultaneous base modification detection with compact devices. Rapid-CNS2- rapid, comprehensive adaptive sampling based pipeline time 5 days was previously described. ad-hoc methylation model...
Abstract BACKGROUND The WHO classification 2021 includes multiple molecular markers for routine diagnostics in addition to histology. Sequencing setup complete profiling requires considerable investment, while batching samples sequencing and methylation can delay turnaround time. We introduce RAPID-CNS2, a nanopore adaptive pipeline that enables comprehensive mutational, copy number of CNS tumours with single third generation assay. It be run offers highly flexible target selection requiring...
Abstract Background The 2021 WHO classification of central nervous system tumors includes multiple molecular markers and patterns that are recommended for routine diagnostic use in addition to histology. Sequencing infrastructures complete profiling require considerable investment, while batching samples sequencing methylation can delay turnaround time. We introduce RAPID-CNS 2 , a nanopore adaptive pipeline enables comprehensive mutational, copy number CNS tumours with single,...
Background: In meningiomas, CDKN2A/B deletions are associated with poor outcomes but rare in most cohorts (1-5%). Large molecular datasets therefore required to explore these and their relationship other prognostic CDKN2A alterations. Methods: We utilized multidimensional data of 560 meningiomas from 5 independent comprehensively interrogate the spectrum alterations through DNA methylation, copy number variation, transcriptomics, proteomics using an integrated approach. Results: Meningiomas...
Abstract BTFC travel award recipient In meningiomas, CDKN2A/B deletions are associated with poor clinical outcomes but exceeding rare in most cohorts (1-5% of cases). Large molecular datasets therefore required to explore these and their relationship other CDKN2A alterations that may be more common, also prognostic on a transcriptomic, epigenomic, and/or copy number level. METHODS: We used multidimensional data 560 meningioma samples from 5 independent comprehensively interrogate the...
Abstract BACKGROUND The WHO classification of CNS tumours 2021 recommends reporting a wide range molecular alterations for WHO-compatible diagnoses. Conventional diagnostic workflows warrant considerable investment and long turnaround times limited by batching. Nanopore sequencing enables read sequencing, real-time targeting simultaneous base modification detection with compact devices. Rapid-CNS2- rapid, comprehensive adaptive sampling based pipeline time 5 days was previously described....
Abstract BACKGROUND Meningiomas arise from the leptomeninges of brain and spinal cord. Despite being most common intracranial tumor in adults, risk stratification remains challenging. Currently, tumors are graded based on histology as well molecular markers. In recent years, several epigenomic classification systems with a correlation to patient outcome have been proposed for meningiomas. However, these do not discriminate between effects microenvironment itself or consider distinct...
Abstract Background Therapy resistance and infiltration still pose major challenges in the treatment of glioma. In tumour border niche, an interaction between different healthy cell types malignant cells leads to therapy resistance, acquisition stem-cell like features, recurrence. However, studying is quite challenging due lack specific glioma markers. Although single datasets contain information about abundance types, they spatial arrangement at niche. Spatial transcriptomic approaches...
Abstract BACKGROUND Integrative brain tumour diagnostics indisputably requires comprehensive reporting of molecular markers. The 2021 WHO classification central nervous system (CNS) tumours substantially increased the set markers for routine evaluation, with greater significance to DNA methylation analysis in diagnostics. Limited by investment and batching, smaller labs clinics might suffer major delays delivering clinical decisions. To make precision accessible, we introduce an integrated...
Abstract BACKGROUND As the most common intracranial tumor, meningiomas have caused increasing interest in field of medical research. Based on their mutational profile, can be separated into two main groups: NF2 altered meningiomas, which occur at WHO grades 1 to 3, and non-NF2 mutant with mutations other genes, such as TRAF7, AKT1, KLF4, SMO, are usually grade 1. While this means that follow a benign course, risk stratification for remains difficult. now, underlying mechanisms contributing...
Abstract BACKGROUND The WHO classification 2021 includes multiple molecular markers for routine diagnostics in addition to histology. Sequencing setup complete profiling requires considerable investment, while batching samples sequencing and methylation can delay turnaround time. We introduce RAPID-CNS2, a nanopore adaptive pipeline that enables comprehensive mutational, copy number of CNS tumours with single third generation assay. It be run offers highly flexible target selection requiring...