Rapid intraoperative amplicon sequencing of CNS tumor markers

Currently, central nervous system tumors are diagnosed with an integrated diagnostic approach that combines histopathological examination with molecular genetic profiling, which requires days to weeks to achieve a precise and informative classification of CNS tumors. This study demonstrates the feas...

Full description

Saved in:
Bibliographic Details
Main Authors: Maximilian Evers, Björn Brändl, Christian Rohrandt, Carolin Kubelt-Kwamin, Franz-Josef Müller, Dominik Danso, André Maicher, Gaojianyong Wang, Sönke Friedrichsen, Stephan Kolkenbrock
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037024003787
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850250617883197440
author Maximilian Evers
Björn Brändl
Christian Rohrandt
Carolin Kubelt-Kwamin
Franz-Josef Müller
Dominik Danso
André Maicher
Gaojianyong Wang
Sönke Friedrichsen
Stephan Kolkenbrock
author_facet Maximilian Evers
Björn Brändl
Christian Rohrandt
Carolin Kubelt-Kwamin
Franz-Josef Müller
Dominik Danso
André Maicher
Gaojianyong Wang
Sönke Friedrichsen
Stephan Kolkenbrock
author_sort Maximilian Evers
collection DOAJ
description Currently, central nervous system tumors are diagnosed with an integrated diagnostic approach that combines histopathological examination with molecular genetic profiling, which requires days to weeks to achieve a precise and informative classification of CNS tumors. This study demonstrates the feasibility of rapid multiplex amplicon nanopore sequencing for identifying critical mutations relevant to molecular stratification of brain tumors within the timeframe of standard resection surgery. Utilizing live analysis of nanopore sequencing data, we evaluated the brain tumor-associated molecular markers IDH1 R132, IDH2 R172, pTERT C228 and C250, H3F3A K27 and G34, Hist1H3B K27, and BRAF V600. Our method achieved a turnaround time of 105 min at the point-of-care from receipt of a tumor biopsy to result with the potential to impact surgical strategy. Our approach can be integrated with recently developed DNA methylation-based diagnostic classification systems, corroborating diagnoses and even further specifying tumor grades, thus enabling a multimodal diagnostic intraoperative assessment of CNS malignancies.
format Article
id doaj-art-7eaf4e7f59c545a88858bb85efca6081
institution OA Journals
issn 2001-0370
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series Computational and Structural Biotechnology Journal
spelling doaj-art-7eaf4e7f59c545a88858bb85efca60812025-08-20T01:58:08ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-0126515710.1016/j.csbj.2024.11.007Rapid intraoperative amplicon sequencing of CNS tumor markersMaximilian Evers0Björn Brändl1Christian Rohrandt2Carolin Kubelt-Kwamin3Franz-Josef Müller4Dominik Danso5André Maicher6Gaojianyong Wang7Sönke Friedrichsen8Stephan Kolkenbrock9altona Diagnostics GmbH, Hamburg, Germany; Institute of Biology and Biotechnology of Plants, University of Münster, Münster, GermanyDepartment of Psychiatry and Psychotherapy, Christian-Albrechts-Universität zu Kiel, Kiel, GermanyDepartment of Psychiatry and Psychotherapy, Christian-Albrechts-Universität zu Kiel, Kiel, GermanyDepartment of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, Kiel, GermanyDepartment of Psychiatry and Psychotherapy, Christian-Albrechts-Universität zu Kiel, Kiel, Germany; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germanyaltona Diagnostics GmbH, Hamburg, Germanyaltona Diagnostics GmbH, Hamburg, GermanyDepartment of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germanyaltona Diagnostics GmbH, Hamburg, Germanyaltona Diagnostics GmbH, Hamburg, Germany; Correspondence to: Stephan Kolkenbrock, altona Diagnostics GmbH, Hamburg, Hamburg, Germany.Currently, central nervous system tumors are diagnosed with an integrated diagnostic approach that combines histopathological examination with molecular genetic profiling, which requires days to weeks to achieve a precise and informative classification of CNS tumors. This study demonstrates the feasibility of rapid multiplex amplicon nanopore sequencing for identifying critical mutations relevant to molecular stratification of brain tumors within the timeframe of standard resection surgery. Utilizing live analysis of nanopore sequencing data, we evaluated the brain tumor-associated molecular markers IDH1 R132, IDH2 R172, pTERT C228 and C250, H3F3A K27 and G34, Hist1H3B K27, and BRAF V600. Our method achieved a turnaround time of 105 min at the point-of-care from receipt of a tumor biopsy to result with the potential to impact surgical strategy. Our approach can be integrated with recently developed DNA methylation-based diagnostic classification systems, corroborating diagnoses and even further specifying tumor grades, thus enabling a multimodal diagnostic intraoperative assessment of CNS malignancies.http://www.sciencedirect.com/science/article/pii/S2001037024003787CNS tumorsAmplicon sequencingTumor markersNanoporeIntraoperative
spellingShingle Maximilian Evers
Björn Brändl
Christian Rohrandt
Carolin Kubelt-Kwamin
Franz-Josef Müller
Dominik Danso
André Maicher
Gaojianyong Wang
Sönke Friedrichsen
Stephan Kolkenbrock
Rapid intraoperative amplicon sequencing of CNS tumor markers
Computational and Structural Biotechnology Journal
CNS tumors
Amplicon sequencing
Tumor markers
Nanopore
Intraoperative
title Rapid intraoperative amplicon sequencing of CNS tumor markers
title_full Rapid intraoperative amplicon sequencing of CNS tumor markers
title_fullStr Rapid intraoperative amplicon sequencing of CNS tumor markers
title_full_unstemmed Rapid intraoperative amplicon sequencing of CNS tumor markers
title_short Rapid intraoperative amplicon sequencing of CNS tumor markers
title_sort rapid intraoperative amplicon sequencing of cns tumor markers
topic CNS tumors
Amplicon sequencing
Tumor markers
Nanopore
Intraoperative
url http://www.sciencedirect.com/science/article/pii/S2001037024003787
work_keys_str_mv AT maximilianevers rapidintraoperativeampliconsequencingofcnstumormarkers
AT bjornbrandl rapidintraoperativeampliconsequencingofcnstumormarkers
AT christianrohrandt rapidintraoperativeampliconsequencingofcnstumormarkers
AT carolinkubeltkwamin rapidintraoperativeampliconsequencingofcnstumormarkers
AT franzjosefmuller rapidintraoperativeampliconsequencingofcnstumormarkers
AT dominikdanso rapidintraoperativeampliconsequencingofcnstumormarkers
AT andremaicher rapidintraoperativeampliconsequencingofcnstumormarkers
AT gaojianyongwang rapidintraoperativeampliconsequencingofcnstumormarkers
AT sonkefriedrichsen rapidintraoperativeampliconsequencingofcnstumormarkers
AT stephankolkenbrock rapidintraoperativeampliconsequencingofcnstumormarkers