Klin Padiatr 2023; 235(06): 378-379
DOI: 10.1055/s-0043-1774766
Abstracts

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

Authors

  • M Simon

    1   Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
    6   authors contributed equally

  • L P Kuschel

    2   Charité-Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany
    6   authors contributed equally

  • K von Hoff

    1   Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany
    3   Department of Paediatric and Adolescent Medicine, Aarhus University Hospital,Aarhus, Denmark

  • P Hernáiz Driever

    1   Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Pediatric Oncology and Hematology, Berlin, Germany

  • E G Hain

    4   Charité-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany

  • A Koch

    4   Charité-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany

  • D Capper

    4   Charité-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany

  • M Schulz

    5   Charité-Universitätsmedizin Berlin, Department of Pediatric Neurosurgery, Berlin, Germany

  • U W Thomale

    5   Charité-Universitätsmedizin Berlin, Department of Pediatric Neurosurgery, Berlin, Germany
    6   authors contributed equally

  • P Euskirchen

    2   Charité-Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany
    6   authors contributed equally
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Background Cavitating ultrasonic aspirator (CUSA) devices are commonly used in neurosurgical procedures to carefully debulk tumor from adjacent healthy brain tissue. Here, we explore the feasibility of using ultrasonic minced tumor tissue to classify otherwise discarded sample material by DNA methylation according to the respective World Health Organization Classification of Tumors of the Central Nervous System using low pass nanopore whole genome sequencing.

Methods 21 ultrasonic aspirated specimens from patients undergoing surgery in the department of pediatric neurosurgery at the Charité –Universitätsmedizin Berlin with either newly diagnosed cerebral lesions or pre-treated lesions were processed by nanopore sequencing to generate copy number profiles and ad-hoc random forest classification. Results were compared to microarray-based routine profiling. Tumor purity was assessed.

Results In 19/21 (90.5 %) samples the minimum amount of 1,000 CpG sites were sequenced. In 20/21 (95.2 %) cases copy number variation profiles could be generated and matched microarray derived copy number profiles, allowing for identification of diagnostically or therapeutically relevant pathognomonic alterations. 12/17 (70.6 %) samples were concordantly classified to the corresponding microarray-based diagnosis by routine neuropathological workup. Applying the recently defined threshold for nanopore-based classification resulted in sensitivity of 64.7 % and specificity of 100 %.

Conclusion CUSA referred sample material of pediatric brain tumors allows for methylation-based classification according to the respective WHO classification of CNS tumors with acceptable sensitivity and high specificity. Hereby, a promising opportunity for accurate classification of pediatric brain tumors by a time- and cost-efficient advanced molecular technique is offered from otherwise discarded tumor tissue.



Publication History

Article published online:
09 November 2023

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