Detection of H3F3A K27M or BRAF V600E in liquid biopsies of
brain tumor patients as diagnostic and monitoring biomarker:
impact of tumor localization and sampling method

J 2025

Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method

MADLENER, Sibylle; Natalia STEPIEN; Daniel SENFTER; Lisa MAYR; Anna LAEMMERER et al.

Základní údaje

Originální název

Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method

Autoři

Vydání

Acta Neuropathologica, New York, Springer, 2025, 0001-6322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.300 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00140615

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Liquid biopsy; Glioma; Longitudinal monitoring; Targeted therapy; Droplet digital PCR; CSF sampling site

Štítky

14110321, 14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 2. 2026 12:27, Mgr. Eva Suchánková

Anotace

V originále

Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management. However, the optimal strategy for monitoring gliomas by LB remains to be determined. In this study, we analyzed circulating tumor DNA (ctDNA) from 78 liquid biopsies (plasma n = 44, cerebrospinal fluid n = 34 (CSF)) of 35 glioma patients, determining H3F3A K28M (K27M) and BRAF V600E mutation allele frequency using droplet digital PCR (ddPCR). All results were correlated to clinically relevant parameters including diagnostic imaging and CSF aspiration site (ventricular vs lumbar) with respect to tumor localization. Regarding diagnostic accuracy, the calculated sensitivity score in the H3F3A K27M cohort was 84.61% for CSF and 73.68% for plasma. In the BRAF V600E cohort, we determined a sensitivity of 83.3% in plasma and 80% in CSF. The overall specificity was 100%. With respect to the CSF aspiration, the intra-operatively obtained CSF demonstrated 100% detection rate, followed by ventricular CSF obtained via Ommaya Reservoir/shunt puncture (93%) and CSF obtained via lumbar puncture (66%). Notably, this further correlated with the proximity of the CSF site to tumor localization. Longitudinal CSF monitoring demonstrated a good correlation to clinical and radiological disease evolution. Importantly, we show for the first time that monitoring BRAF V600E by ddPCR could serve as treatment response assessment in gliomas. In summary, our observation may inform recommendations with regard to location of CSF aspiration when incorporating LB into future treatment protocols.

Návaznosti

MUNI/A/1764/2024, interní kód MU

Název: Personalizovaná léčba v dětské onkologii: molekulární podstata nádorů

Investor: Masarykova univerzita, Personalizovaná léčba v dětské onkologii: molekulární podstata nádorů

90249, velká výzkumná infrastruktura

Název: CZECRIN IV

Citovat

MADLENER, Sibylle; Natalia STEPIEN; Daniel SENFTER; Lisa MAYR; Anna LAEMMERER; Cora HEDRICH; Alicia BAUMGARTNER; Daniela LOETSCH-GOJO; Jaroslav ŠTĚRBA; Petra POKORNÁ; Barbara KIESEL; Georg WIDHALM; Franziska ECKERT; Matthias PREUSSER; Karl ROESSLER; Amedeo AZIZI; Andreas PEYRL; Thomas CZECH; Christine HABERLER; Irene SLAVC; Gregor KASPRIAN; Christian DORFER; Julia FURTNER a Johannes GOJO. Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method. Acta Neuropathologica. New York: Springer, 2025, roč. 149, č. 1, s. 1-12. ISSN 0001-6322. Dostupné z: https://doi.org/10.1007/s00401-024-02842-7.

@article{2474800,
   author = {Madlener, Sibylle and Stepien, Natalia and Senfter, Daniel and Mayr, Lisa and Laemmerer, Anna and Hedrich, Cora and Baumgartner, Alicia and LoetschandGojo, Daniela and Štěrba, Jaroslav and Pokorná, Petra and Kiesel, Barbara and Widhalm, Georg and Eckert, Franziska and Preusser, Matthias and Roessler, Karl and Azizi, Amedeo and Peyrl, Andreas and Czech, Thomas and Haberler, Christine and Slavc, Irene and Kasprian, Gregor and Dorfer, Christian and Furtner, Julia and Gojo, Johannes},
   article_location = {New York},
   article_number = {1},
   doi = {https://doi.org/10.1007/s00401-024-02842-7},
   keywords = {Liquid biopsy; Glioma; Longitudinal monitoring; Targeted therapy; Droplet digital PCR; CSF sampling site},
   language = {eng},
   issn = {0001-6322},
   journal = {Acta Neuropathologica},
   title = {Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method},
   url = {https://link.springer.com/article/10.1007/s00401-024-02842-7},
   volume = {149},
   year = {2025}
}

TY  - JOUR
ID  - 2474800
AU  - Madlener, Sibylle - Stepien, Natalia - Senfter, Daniel - Mayr, Lisa - Laemmerer, Anna - Hedrich, Cora - Baumgartner, Alicia - Loetsch-Gojo, Daniela - Štěrba, Jaroslav - Pokorná, Petra - Kiesel, Barbara - Widhalm, Georg - Eckert, Franziska - Preusser, Matthias - Roessler, Karl - Azizi, Amedeo - Peyrl, Andreas - Czech, Thomas - Haberler, Christine - Slavc, Irene - Kasprian, Gregor - Dorfer, Christian - Furtner, Julia - Gojo, Johannes
PY  - 2025
TI  - Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method
JF  - Acta Neuropathologica
VL  - 149
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - Springer
SN  - 00016322
KW  - Liquid biopsy
KW  - Glioma
KW  - Longitudinal monitoring
KW  - Targeted therapy
KW  - Droplet digital PCR
KW  - CSF sampling site
UR  - https://link.springer.com/article/10.1007/s00401-024-02842-7
N2  - Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management. However, the optimal strategy for monitoring gliomas by LB remains to be determined. In this study, we analyzed circulating tumor DNA (ctDNA) from 78 liquid biopsies (plasma n = 44, cerebrospinal fluid n = 34 (CSF)) of 35 glioma patients, determining H3F3A K28M (K27M) and BRAF V600E mutation allele frequency using droplet digital PCR (ddPCR). All results were correlated to clinically relevant parameters including diagnostic imaging and CSF aspiration site (ventricular vs lumbar) with respect to tumor localization. Regarding diagnostic accuracy, the calculated sensitivity score in the H3F3A K27M cohort was 84.61% for CSF and 73.68% for plasma. In the BRAF V600E cohort, we determined a sensitivity of 83.3% in plasma and 80% in CSF. The overall specificity was 100%. With respect to the CSF aspiration, the intra-operatively obtained CSF demonstrated 100% detection rate, followed by ventricular CSF obtained via Ommaya Reservoir/shunt puncture (93%) and CSF obtained via lumbar puncture (66%). Notably, this further correlated with the proximity of the CSF site to tumor localization. Longitudinal CSF monitoring demonstrated a good correlation to clinical and radiological disease evolution. Importantly, we show for the first time that monitoring BRAF V600E by ddPCR could serve as treatment response assessment in gliomas. In summary, our observation may inform recommendations with regard to location of CSF aspiration when incorporating LB into future treatment protocols.
ER  -

MADLENER, Sibylle; Natalia STEPIEN; Daniel SENFTER; Lisa MAYR; Anna LAEMMERER; Cora HEDRICH; Alicia BAUMGARTNER; Daniela LOETSCH-GOJO; Jaroslav ŠTĚRBA; Petra POKORNÁ; Barbara KIESEL; Georg WIDHALM; Franziska ECKERT; Matthias PREUSSER; Karl ROESSLER; Amedeo AZIZI; Andreas PEYRL; Thomas CZECH; Christine HABERLER; Irene SLAVC; Gregor KASPRIAN; Christian DORFER; Julia FURTNER a Johannes GOJO. Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method. \textit{Acta Neuropathologica}. New York: Springer, 2025, roč.~149, č.~1, s.~1-12. ISSN~0001-6322. Dostupné z: https://doi.org/10.1007/s00401-024-02842-7.

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