Rapid DNA methylation-based classification of pediatric brain tumors from ultrasonic aspirate specimens.

Autor: Simon M; Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany., Kuschel LP; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany., von Hoff K; Department of Paediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark., Yuan D; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany., Hernáiz Driever P; Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany., Hain EG; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany., Koch A; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany., Capper D; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, Berlin, Germany., Schulz M; Department of Pediatric Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany., Thomale UW; Department of Pediatric Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany., Euskirchen P; Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany. philipp.euskirchen@charite.de.; Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany. philipp.euskirchen@charite.de.; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, Berlin, Germany. philipp.euskirchen@charite.de.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2024 Aug; Vol. 169 (1), pp. 73-83. Date of Electronic Publication: 2024 May 21.
DOI: 10.1007/s11060-024-04702-6
Abstrakt: Background: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing.
Methods: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation.
Results: 19 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 17/19 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 79%. Copy number variation profiles were generated for all cases and matched EPIC results in 18/19 (95%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations.
Conclusion: Methylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing.
(© 2024. The Author(s).)
Databáze: MEDLINE
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