Clinical Chemistry

, volume 70 , issue 1

Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid

Ann Kristin Afflerbach ^{1, 2}

Christian Rohrandt ³

Björn Brändl ⁴

Marthe Sönksen ¹

Jürgen Hench ⁵

Stephan Frank ⁵

Daniela Börnigen ⁶

Alawi Malik ⁶

Martin Mynarek ¹

Beate Winkler ¹

U. Schuller ⁷

Michael Synowitz ⁸

Lasse Dührsen ⁷

Stefan Rutkowski ¹

Annika Wefers ^{9, 10}

Franz Josef Müller ^{4, 11}

Melanie Schoof ^{1, 2}

Ulrich Schüller ^{1, 2, 9}

Hide authors affiliations Show authors affiliations: 11 affiliations

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany |

Research Institute Children’s Cancer Center Hamburg , Hamburg , Germany |

Institute for Communications Technologies and Embedded Systems, University of Applied Sciences Kiel , Kiel , Germany |

⁴

Center for Integrative Psychiatry, University Hospital Schleswig-Holstein , Kiel , Germany |

⁵

Department of Pathology, University Hospital Basel , Basel , Switzerland |

⁶

Bioinformatics Core, University Medical Center Hamburg-Eppendorf , Hamburg , Germany |

⁷

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf , Hamburg , Germany |

⁸

Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel , Kiel , Germany |

⁹

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany |

¹⁰

Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg- Eppendorf , Hamburg , Germany |

¹¹

Department of Genome Regulation, Max Planck Institute for Molecular Genetics Berlin , Berlin , Germany |

Publication type: Journal Article

Publication date: 2023-08-25

American Association for Clinical Chemistry

Clinical Chemistry

scimago Q1

wos Q1

SJR: 1.345

CiteScore: 9.7

Impact factor: 6.3

ISSN: 00099147, 15308561

DOI: 10.1093/clinchem/hvad115

Copy DOI

PubMed ID: 37624932

Clinical Biochemistry

Biochemistry (medical)

Abstract

Background

Molecular brain tumor diagnosis is usually dependent on tissue biopsies or resections. This can pose several risks associated with anesthesia or neurosurgery, especially for lesions in the brain stem or other difficult-to-reach anatomical sites. Apart from initial diagnosis, tumor progression, recurrence, or the acquisition of novel genetic alterations can only be proven by re-biopsies.

Methods

We employed Nanopore sequencing on cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and analyzed copy number variations (CNV) and global DNA methylation using a random forest classifier. We sequenced 129 samples with sufficient DNA. These samples came from 99 patients and encompassed 22 entities. Results were compared to clinical diagnosis and molecular analysis of tumor tissue, if available.

Results

110/129 samples were technically successful, and 50 of these contained detectable circulating tumor DNA (ctDNA) by CNV or methylation profiling. ctDNA was detected in samples from patients with progressive disease but also from patients without known residual disease. CNV plots showed diagnostic and prognostic alterations, such as C19MC amplifications in embryonal tumors with multilayered rosettes or Chr.1q gains and Chr.6q losses in posterior fossa group A ependymoma, respectively. Most CNV profiles mirrored the profiles of the respective tumor tissue. DNA methylation allowed exact classification of the tumor in 22/110 cases and led to incorrect classification in 2/110 cases. Only 5/50 samples with detected ctDNA contained tumor cells detectable through microscopy.

Conclusions

Our results suggest that Nanopore sequencing data of cfDNA from CSF samples may be a promising approach for initial brain tumor diagnostics and an important tool for disease monitoring.

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GOST |

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GOST Copy

Afflerbach A. K. et al. Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid // Clinical Chemistry. 2023. Vol. 70. No. 1.

GOST all authors (up to 50) Copy

Afflerbach A. K., Rohrandt C., Brändl B., Sönksen M., Hench J., Frank S., Börnigen D., Malik A., Mynarek M., Winkler B., Schuller U., Synowitz M., Dührsen L., Rutkowski S., Wefers A., Müller F. J., Schoof M., Schüller U. Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid // Clinical Chemistry. 2023. Vol. 70. No. 1.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1093/clinchem/hvad115

UR - https://doi.org/10.1093/clinchem/hvad115

TI - Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid

T2 - Clinical Chemistry

AU - Afflerbach, Ann Kristin

AU - Rohrandt, Christian

AU - Brändl, Björn

AU - Sönksen, Marthe

AU - Hench, Jürgen

AU - Frank, Stephan

AU - Börnigen, Daniela

AU - Malik, Alawi

AU - Mynarek, Martin

AU - Winkler, Beate

AU - Schuller, U.

AU - Synowitz, Michael

AU - Dührsen, Lasse

AU - Rutkowski, Stefan

AU - Wefers, Annika

AU - Müller, Franz Josef

AU - Schoof, Melanie

AU - Schüller, Ulrich

PY - 2023

DA - 2023/08/25

PB - American Association for Clinical Chemistry

IS - 1

VL - 70

PMID - 37624932

SN - 0009-9147

SN - 1530-8561

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2023_Afflerbach,

author = {Ann Kristin Afflerbach and Christian Rohrandt and Björn Brändl and Marthe Sönksen and Jürgen Hench and Stephan Frank and Daniela Börnigen and Alawi Malik and Martin Mynarek and Beate Winkler and U. Schuller and Michael Synowitz and Lasse Dührsen and Stefan Rutkowski and Annika Wefers and Franz Josef Müller and Melanie Schoof and Ulrich Schüller},

title = {Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid},

journal = {Clinical Chemistry},

year = {2023},

volume = {70},

publisher = {American Association for Clinical Chemistry},

month = {aug},

url = {https://doi.org/10.1093/clinchem/hvad115},

number = {1},

doi = {10.1093/clinchem/hvad115}

}

Publisher

American Association for Clinical Chemistry

Journal

Clinical Chemistry

scimago Q1

wos Q1

SJR

1.345

CiteScore

9.7

Impact factor

6.3

ISSN

00099147 (Print)

15308561 (Electronic)

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