Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors

Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with centra...
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Autor*in:	Hickman, Richard A. [verfasserIn] Miller, Alexandra M. [verfasserIn] Holle, Bridget M. [verfasserIn] Jee, Justin [verfasserIn] Liu, Si-Yang [verfasserIn] Ross, Dara [verfasserIn] Yu, Helena [verfasserIn] Riely, Gregory J. [verfasserIn] Ombres, Christina [verfasserIn] Gewirtz, Alexandra N. [verfasserIn] Reiner, Anne S. [verfasserIn] Nandakumar, Subhiksha [verfasserIn] Price, Adam [verfasserIn] Kaley, Thomas J. [verfasserIn] Graham, Maya S. [verfasserIn] Vanderbilt, Chad [verfasserIn] Rana, Satshil [verfasserIn] Hill, Katherine [verfasserIn] Chabot, Kiana [verfasserIn] Campos, Carl [verfasserIn] Nafa, Khedoudja [verfasserIn] Shukla, Neerav [verfasserIn] Karajannis, Matthias [verfasserIn] Li, Bob [verfasserIn] Berger, Michael [verfasserIn] Ladanyi, Marc [verfasserIn] Pentsova, Elena [verfasserIn] Boire, Adrienne [verfasserIn] Brannon, A. Rose [verfasserIn] Bale, Tejus [verfasserIn] Mellinghoff, Ingo K. [verfasserIn] Arcila, Maria E. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Acta Neuropathologica Communications - BioMed Central, 2013, 12(2024), 1 vom: 17. Sept.
Übergeordnetes Werk:	volume:12 ; year:2024 ; number:1 ; day:17 ; month:09

Links:	Volltext

DOI / URN:	10.1186/s40478-024-01846-4

Katalog-ID:	SPR057357560

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allfields	10.1186/s40478-024-01846-4 doi (DE-627)SPR057357560 (SPR)s40478-024-01846-4-e DE-627 ger DE-627 rakwb eng 610 VZ Hickman, Richard A. verfasserin (orcid)0000-0002-8329-6083 aut Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. Miller, Alexandra M. verfasserin aut Holle, Bridget M. verfasserin aut Jee, Justin verfasserin aut Liu, Si-Yang verfasserin aut Ross, Dara verfasserin aut Yu, Helena verfasserin aut Riely, Gregory J. verfasserin aut Ombres, Christina verfasserin aut Gewirtz, Alexandra N. verfasserin aut Reiner, Anne S. verfasserin aut Nandakumar, Subhiksha verfasserin aut Price, Adam verfasserin aut Kaley, Thomas J. verfasserin aut Graham, Maya S. verfasserin aut Vanderbilt, Chad verfasserin aut Rana, Satshil verfasserin aut Hill, Katherine verfasserin aut Chabot, Kiana verfasserin aut Campos, Carl verfasserin aut Nafa, Khedoudja verfasserin aut Shukla, Neerav verfasserin aut Karajannis, Matthias verfasserin aut Li, Bob verfasserin aut Berger, Michael verfasserin aut Ladanyi, Marc verfasserin aut Pentsova, Elena verfasserin aut Boire, Adrienne verfasserin aut Brannon, A. Rose verfasserin aut Bale, Tejus verfasserin aut Mellinghoff, Ingo K. verfasserin aut Arcila, Maria E. verfasserin aut Enthalten in Acta Neuropathologica Communications BioMed Central, 2013 12(2024), 1 vom: 17. Sept. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:12 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1186/s40478-024-01846-4 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 1 17 09
spelling	10.1186/s40478-024-01846-4 doi (DE-627)SPR057357560 (SPR)s40478-024-01846-4-e DE-627 ger DE-627 rakwb eng 610 VZ Hickman, Richard A. verfasserin (orcid)0000-0002-8329-6083 aut Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. Miller, Alexandra M. verfasserin aut Holle, Bridget M. verfasserin aut Jee, Justin verfasserin aut Liu, Si-Yang verfasserin aut Ross, Dara verfasserin aut Yu, Helena verfasserin aut Riely, Gregory J. verfasserin aut Ombres, Christina verfasserin aut Gewirtz, Alexandra N. verfasserin aut Reiner, Anne S. verfasserin aut Nandakumar, Subhiksha verfasserin aut Price, Adam verfasserin aut Kaley, Thomas J. verfasserin aut Graham, Maya S. verfasserin aut Vanderbilt, Chad verfasserin aut Rana, Satshil verfasserin aut Hill, Katherine verfasserin aut Chabot, Kiana verfasserin aut Campos, Carl verfasserin aut Nafa, Khedoudja verfasserin aut Shukla, Neerav verfasserin aut Karajannis, Matthias verfasserin aut Li, Bob verfasserin aut Berger, Michael verfasserin aut Ladanyi, Marc verfasserin aut Pentsova, Elena verfasserin aut Boire, Adrienne verfasserin aut Brannon, A. Rose verfasserin aut Bale, Tejus verfasserin aut Mellinghoff, Ingo K. verfasserin aut Arcila, Maria E. verfasserin aut Enthalten in Acta Neuropathologica Communications BioMed Central, 2013 12(2024), 1 vom: 17. Sept. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:12 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1186/s40478-024-01846-4 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 1 17 09
allfields_unstemmed	10.1186/s40478-024-01846-4 doi (DE-627)SPR057357560 (SPR)s40478-024-01846-4-e DE-627 ger DE-627 rakwb eng 610 VZ Hickman, Richard A. verfasserin (orcid)0000-0002-8329-6083 aut Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. Miller, Alexandra M. verfasserin aut Holle, Bridget M. verfasserin aut Jee, Justin verfasserin aut Liu, Si-Yang verfasserin aut Ross, Dara verfasserin aut Yu, Helena verfasserin aut Riely, Gregory J. verfasserin aut Ombres, Christina verfasserin aut Gewirtz, Alexandra N. verfasserin aut Reiner, Anne S. verfasserin aut Nandakumar, Subhiksha verfasserin aut Price, Adam verfasserin aut Kaley, Thomas J. verfasserin aut Graham, Maya S. verfasserin aut Vanderbilt, Chad verfasserin aut Rana, Satshil verfasserin aut Hill, Katherine verfasserin aut Chabot, Kiana verfasserin aut Campos, Carl verfasserin aut Nafa, Khedoudja verfasserin aut Shukla, Neerav verfasserin aut Karajannis, Matthias verfasserin aut Li, Bob verfasserin aut Berger, Michael verfasserin aut Ladanyi, Marc verfasserin aut Pentsova, Elena verfasserin aut Boire, Adrienne verfasserin aut Brannon, A. Rose verfasserin aut Bale, Tejus verfasserin aut Mellinghoff, Ingo K. verfasserin aut Arcila, Maria E. verfasserin aut Enthalten in Acta Neuropathologica Communications BioMed Central, 2013 12(2024), 1 vom: 17. Sept. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:12 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1186/s40478-024-01846-4 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 1 17 09
allfieldsGer	10.1186/s40478-024-01846-4 doi (DE-627)SPR057357560 (SPR)s40478-024-01846-4-e DE-627 ger DE-627 rakwb eng 610 VZ Hickman, Richard A. verfasserin (orcid)0000-0002-8329-6083 aut Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. Miller, Alexandra M. verfasserin aut Holle, Bridget M. verfasserin aut Jee, Justin verfasserin aut Liu, Si-Yang verfasserin aut Ross, Dara verfasserin aut Yu, Helena verfasserin aut Riely, Gregory J. verfasserin aut Ombres, Christina verfasserin aut Gewirtz, Alexandra N. verfasserin aut Reiner, Anne S. verfasserin aut Nandakumar, Subhiksha verfasserin aut Price, Adam verfasserin aut Kaley, Thomas J. verfasserin aut Graham, Maya S. verfasserin aut Vanderbilt, Chad verfasserin aut Rana, Satshil verfasserin aut Hill, Katherine verfasserin aut Chabot, Kiana verfasserin aut Campos, Carl verfasserin aut Nafa, Khedoudja verfasserin aut Shukla, Neerav verfasserin aut Karajannis, Matthias verfasserin aut Li, Bob verfasserin aut Berger, Michael verfasserin aut Ladanyi, Marc verfasserin aut Pentsova, Elena verfasserin aut Boire, Adrienne verfasserin aut Brannon, A. Rose verfasserin aut Bale, Tejus verfasserin aut Mellinghoff, Ingo K. verfasserin aut Arcila, Maria E. verfasserin aut Enthalten in Acta Neuropathologica Communications BioMed Central, 2013 12(2024), 1 vom: 17. Sept. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:12 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1186/s40478-024-01846-4 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 1 17 09
allfieldsSound	10.1186/s40478-024-01846-4 doi (DE-627)SPR057357560 (SPR)s40478-024-01846-4-e DE-627 ger DE-627 rakwb eng 610 VZ Hickman, Richard A. verfasserin (orcid)0000-0002-8329-6083 aut Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. Miller, Alexandra M. verfasserin aut Holle, Bridget M. verfasserin aut Jee, Justin verfasserin aut Liu, Si-Yang verfasserin aut Ross, Dara verfasserin aut Yu, Helena verfasserin aut Riely, Gregory J. verfasserin aut Ombres, Christina verfasserin aut Gewirtz, Alexandra N. verfasserin aut Reiner, Anne S. verfasserin aut Nandakumar, Subhiksha verfasserin aut Price, Adam verfasserin aut Kaley, Thomas J. verfasserin aut Graham, Maya S. verfasserin aut Vanderbilt, Chad verfasserin aut Rana, Satshil verfasserin aut Hill, Katherine verfasserin aut Chabot, Kiana verfasserin aut Campos, Carl verfasserin aut Nafa, Khedoudja verfasserin aut Shukla, Neerav verfasserin aut Karajannis, Matthias verfasserin aut Li, Bob verfasserin aut Berger, Michael verfasserin aut Ladanyi, Marc verfasserin aut Pentsova, Elena verfasserin aut Boire, Adrienne verfasserin aut Brannon, A. Rose verfasserin aut Bale, Tejus verfasserin aut Mellinghoff, Ingo K. verfasserin aut Arcila, Maria E. verfasserin aut Enthalten in Acta Neuropathologica Communications BioMed Central, 2013 12(2024), 1 vom: 17. Sept. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:12 year:2024 number:1 day:17 month:09 https://dx.doi.org/10.1186/s40478-024-01846-4 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2024 1 17 09
language	English
source	Enthalten in Acta Neuropathologica Communications 12(2024), 1 vom: 17. Sept. volume:12 year:2024 number:1 day:17 month:09
sourceStr	Enthalten in Acta Neuropathologica Communications 12(2024), 1 vom: 17. Sept. volume:12 year:2024 number:1 day:17 month:09
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container_title	Acta Neuropathologica Communications
authorswithroles_txt_mv	Hickman, Richard A. @@aut@@ Miller, Alexandra M. @@aut@@ Holle, Bridget M. @@aut@@ Jee, Justin @@aut@@ Liu, Si-Yang @@aut@@ Ross, Dara @@aut@@ Yu, Helena @@aut@@ Riely, Gregory J. @@aut@@ Ombres, Christina @@aut@@ Gewirtz, Alexandra N. @@aut@@ Reiner, Anne S. @@aut@@ Nandakumar, Subhiksha @@aut@@ Price, Adam @@aut@@ Kaley, Thomas J. @@aut@@ Graham, Maya S. @@aut@@ Vanderbilt, Chad @@aut@@ Rana, Satshil @@aut@@ Hill, Katherine @@aut@@ Chabot, Kiana @@aut@@ Campos, Carl @@aut@@ Nafa, Khedoudja @@aut@@ Shukla, Neerav @@aut@@ Karajannis, Matthias @@aut@@ Li, Bob @@aut@@ Berger, Michael @@aut@@ Ladanyi, Marc @@aut@@ Pentsova, Elena @@aut@@ Boire, Adrienne @@aut@@ Brannon, A. Rose @@aut@@ Bale, Tejus @@aut@@ Mellinghoff, Ingo K. @@aut@@ Arcila, Maria E. @@aut@@
publishDateDaySort_date	2024-09-17T00:00:00Z
hierarchy_top_id	746066465
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title	Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
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title_full	Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
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title_sort	real-world experience with circulating tumor dna in cerebrospinal fluid from patients with central nervous system tumors
title_auth	Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
abstract	Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. © The Author(s) 2024
abstractGer	Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. © The Author(s) 2024
abstract_unstemmed	Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors. © The Author(s) 2024
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title_short	Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
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author2	Miller, Alexandra M. Holle, Bridget M. Jee, Justin Liu, Si-Yang Ross, Dara Yu, Helena Riely, Gregory J. Ombres, Christina Gewirtz, Alexandra N. Reiner, Anne S. Nandakumar, Subhiksha Price, Adam Kaley, Thomas J. Graham, Maya S. Vanderbilt, Chad Rana, Satshil Hill, Katherine Chabot, Kiana Campos, Carl Nafa, Khedoudja Shukla, Neerav Karajannis, Matthias Li, Bob Berger, Michael Ladanyi, Marc Pentsova, Elena Boire, Adrienne Brannon, A. Rose Bale, Tejus Mellinghoff, Ingo K. Arcila, Maria E.
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Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors

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