Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients
Abstract The gold standard for precise diagnostic classification of brain tumors requires tissue sampling, which carries relevant procedural risks. Brain biopsies often have limited sensitivity and fail to address tumor heterogeneity, because small tissue parts are being examined. This study aims to...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-024-01887-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849235639732535296 |
|---|---|
| author | Svenja Klinsing Julia Beck Katharina J. Weber Kirsten Bornemann-Kolatzki Mareike Dettki Hans Urban Bastian Roller Kai U. Chow Henning Reis Peter J. Wild Ekkehard Schuetz Philipp Euskirchen Joachim P. Steinbach Michael W. Ronellenfitsch Patrick N. Harter Pia S. Zeiner |
| author_facet | Svenja Klinsing Julia Beck Katharina J. Weber Kirsten Bornemann-Kolatzki Mareike Dettki Hans Urban Bastian Roller Kai U. Chow Henning Reis Peter J. Wild Ekkehard Schuetz Philipp Euskirchen Joachim P. Steinbach Michael W. Ronellenfitsch Patrick N. Harter Pia S. Zeiner |
| author_sort | Svenja Klinsing |
| collection | DOAJ |
| description | Abstract The gold standard for precise diagnostic classification of brain tumors requires tissue sampling, which carries relevant procedural risks. Brain biopsies often have limited sensitivity and fail to address tumor heterogeneity, because small tissue parts are being examined. This study aims to explore the detection and quantification of diagnostically relevant somatic copy number aberrations (SCNAs) in cell-free DNA (cfDNA) extracted from cerebrospinal fluid (CSF) in a real-world cohort of patients with defined brain tumor subtypes. A total of 33 CSF samples were collected from 30 patients for cfDNA extraction. Shallow whole-genome sequencing was conducted on CSF samples containing > 3ng of cfDNA and corresponding tissue DNA from nine patients. The sequencing cohort encompassed 26 samples of 23 patients, comprising 12 with confirmed CNS cancer as compared to 11 patients with either ambiguous CNS lesions (n = 5) or non-cancer CNS lesions (n = 6). After mapping and quality filtering SCNAs were called by depth-of-coverage analyses with a binning of 5.5 Mbp. SCNAs were exclusively identified in CSF cfDNA from brain tumor patients (10/12, 83%). In tumor patients, SCNAs were detectable in cfDNA from all patients with, but also in five of seven patients without tumor cells detected by CSF cytopathology. A substantial number of shared SCNAs were traceable between tissue and CSF in matched pair analyses. Additionally, some SCNAs unique to either CSF or tissue indicating spatial heterogeneity or tumor evolution. Also, diagnostically relevant genomic alterations as well as essential and desirable SCNAs as implemented in the current WHO classification of CNS tumors for certain primary brain tumor subtypes were traceable. In summary, this minimally invasive cfDNA-based LB approach employing shallow whole genome sequencing demonstrates potential for providing a molecularly informed diagnosis of CNS cancers, mapping tumor heterogeneity, tracking tumor evolution, and surveilling tumor patients. Further prospective trials are warranted. |
| format | Article |
| id | doaj-art-bb49ac9722b644f68630890aba9b3785 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-bb49ac9722b644f68630890aba9b37852025-08-20T04:02:44ZengBMCActa Neuropathologica Communications2051-59602024-11-0112111310.1186/s40478-024-01887-9Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patientsSvenja Klinsing0Julia Beck1Katharina J. Weber2Kirsten Bornemann-Kolatzki3Mareike Dettki4Hans Urban5Bastian Roller6Kai U. Chow7Henning Reis8Peter J. Wild9Ekkehard Schuetz10Philipp Euskirchen11Joachim P. Steinbach12Michael W. Ronellenfitsch13Patrick N. Harter14Pia S. Zeiner15Dr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtChronix Biomedical, OncocyteInstitute of Neurology (Edinger-Institute), University Hospital, Goethe University FrankfurtChronix Biomedical, OncocyteDr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtDr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtDr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtAmbulantes KrebszentrumDr. Senckenberg Institute of Pathology, Goethe University Frankfurt, University HospitalDr. Senckenberg Institute of Pathology, Goethe University Frankfurt, University HospitalChronix Biomedical, OncocyteDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin Und Humboldt Universität Zu BerlinDr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtDr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtInstitute of Neurology (Edinger-Institute), University Hospital, Goethe University FrankfurtDr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University FrankfurtAbstract The gold standard for precise diagnostic classification of brain tumors requires tissue sampling, which carries relevant procedural risks. Brain biopsies often have limited sensitivity and fail to address tumor heterogeneity, because small tissue parts are being examined. This study aims to explore the detection and quantification of diagnostically relevant somatic copy number aberrations (SCNAs) in cell-free DNA (cfDNA) extracted from cerebrospinal fluid (CSF) in a real-world cohort of patients with defined brain tumor subtypes. A total of 33 CSF samples were collected from 30 patients for cfDNA extraction. Shallow whole-genome sequencing was conducted on CSF samples containing > 3ng of cfDNA and corresponding tissue DNA from nine patients. The sequencing cohort encompassed 26 samples of 23 patients, comprising 12 with confirmed CNS cancer as compared to 11 patients with either ambiguous CNS lesions (n = 5) or non-cancer CNS lesions (n = 6). After mapping and quality filtering SCNAs were called by depth-of-coverage analyses with a binning of 5.5 Mbp. SCNAs were exclusively identified in CSF cfDNA from brain tumor patients (10/12, 83%). In tumor patients, SCNAs were detectable in cfDNA from all patients with, but also in five of seven patients without tumor cells detected by CSF cytopathology. A substantial number of shared SCNAs were traceable between tissue and CSF in matched pair analyses. Additionally, some SCNAs unique to either CSF or tissue indicating spatial heterogeneity or tumor evolution. Also, diagnostically relevant genomic alterations as well as essential and desirable SCNAs as implemented in the current WHO classification of CNS tumors for certain primary brain tumor subtypes were traceable. In summary, this minimally invasive cfDNA-based LB approach employing shallow whole genome sequencing demonstrates potential for providing a molecularly informed diagnosis of CNS cancers, mapping tumor heterogeneity, tracking tumor evolution, and surveilling tumor patients. Further prospective trials are warranted.https://doi.org/10.1186/s40478-024-01887-9Cell-free DNACerebrospinal fluidLiquid biopsyNext-generation sequencingBrain tumor |
| spellingShingle | Svenja Klinsing Julia Beck Katharina J. Weber Kirsten Bornemann-Kolatzki Mareike Dettki Hans Urban Bastian Roller Kai U. Chow Henning Reis Peter J. Wild Ekkehard Schuetz Philipp Euskirchen Joachim P. Steinbach Michael W. Ronellenfitsch Patrick N. Harter Pia S. Zeiner Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients Acta Neuropathologica Communications Cell-free DNA Cerebrospinal fluid Liquid biopsy Next-generation sequencing Brain tumor |
| title | Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients |
| title_full | Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients |
| title_fullStr | Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients |
| title_full_unstemmed | Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients |
| title_short | Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients |
| title_sort | detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell free dna in brain tumor patients |
| topic | Cell-free DNA Cerebrospinal fluid Liquid biopsy Next-generation sequencing Brain tumor |
| url | https://doi.org/10.1186/s40478-024-01887-9 |
| work_keys_str_mv | AT svenjaklinsing detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT juliabeck detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT katharinajweber detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT kirstenbornemannkolatzki detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT mareikedettki detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT hansurban detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT bastianroller detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT kaiuchow detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT henningreis detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT peterjwild detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT ekkehardschuetz detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT philippeuskirchen detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT joachimpsteinbach detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT michaelwronellenfitsch detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT patricknharter detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients AT piaszeiner detectionofdiagnosticsomaticcopynumberalterationsfromcerebrospinalfluidcellfreednainbraintumorpatients |