TY  - JOUR
AU  - Erez, Nir
AU  - Furth, Noa
AU  - Fedyuk, Vadim
AU  - Wadden, Jack
AU  - Aittaleb, Rayan
AU  - Adam, Tiffany
AU  - Schwark, Kallen
AU  - Niculcea, Michael
AU  - Miclea, Madeline
AU  - Mody, Rajen
AU  - Franson, Andrea
AU  - Parmar, Hemant A
AU  - Ibrahim, Mohannad
AU  - Lau, Benison
AU  - Eze, Augustine
AU  - Nourmohammadi, Niku
AU  - Fried, Iris
AU  - Nazarian, Javad
AU  - Ron, Guy
AU  - Venneti, Sriram
AU  - Koschmann, Carl
AU  - Shema, Efrat
TI  - Single-molecule systems for the detection and monitoring of plasma-circulating nucleosomes and oncoproteins in diffuse midline glioma.
JO  - Cell reports / Medicine
VL  - 6
IS  - 1
SN  - 2666-3791
CY  - Cambridge, MA
PB  - Cell Press
M1  - DKFZ-2025-02508
SP  - 101918
PY  - 2025
N1  - #DKFZ-MOST-Ca219#
AB  - The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG). The system reveals epigenetic patterns unique to DMG, significantly differentiating this group of patients from healthy subjects or individuals diagnosed with other cancer types. We further develop a method to directly quantify the tumor-originating oncoproteins, lysine 27 to methionine substitution in histone H3 (H3-K27M) and mutant p53, from <1 mL of plasma, allowing for the accurate molecular classification of patients with DMG. We show that our strategy correlates with MRI and droplet-digital PCR (ddPCR) measurements of ctDNA, highlighting the clinical potential of single-molecule-based, multi-parametric assays for DMG diagnosis and treatment monitoring.
KW  - Humans
KW  - Nucleosomes: metabolism
KW  - Glioma: blood
KW  - Glioma: genetics
KW  - Glioma: diagnosis
KW  - Glioma: pathology
KW  - Histones: genetics
KW  - Histones: blood
KW  - Histones: metabolism
KW  - Brain Neoplasms: blood
KW  - Brain Neoplasms: genetics
KW  - Brain Neoplasms: diagnosis
KW  - Biomarkers, Tumor: blood
KW  - Biomarkers, Tumor: genetics
KW  - Male
KW  - Female
KW  - Circulating Tumor DNA: blood
KW  - Tumor Suppressor Protein p53: blood
KW  - Tumor Suppressor Protein p53: genetics
KW  - Single Molecule Imaging: methods
KW  - Adult
KW  - Middle Aged
KW  - DIPG (Other)
KW  - H3-K27M (Other)
KW  - TP53 (Other)
KW  - liquid-biopsy (Other)
KW  - oncohistones (Other)
KW  - single-molecule (Other)
KW  - Nucleosomes (NLM Chemicals)
KW  - Histones (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - Circulating Tumor DNA (NLM Chemicals)
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39809263
C2  - pmc:PMC11866549
DO  - DOI:10.1016/j.xcrm.2024.101918
UR  - https://inrepo02.dkfz.de/record/306282
ER  -