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@ARTICLE{Erez:306282,
author = {N. Erez and N. Furth and V. Fedyuk and J. Wadden and R.
Aittaleb and T. Adam and K. Schwark and M. Niculcea and M.
Miclea and R. Mody and A. Franson and H. A. Parmar and M.
Ibrahim and B. Lau and A. Eze and N. Nourmohammadi and I.
Fried and J. Nazarian and G. Ron and S. Venneti and C.
Koschmann and E. Shema},
title = {{S}ingle-molecule systems for the detection and monitoring
of plasma-circulating nucleosomes and oncoproteins in
diffuse midline glioma.},
journal = {Cell reports / Medicine},
volume = {6},
number = {1},
issn = {2666-3791},
address = {Cambridge, MA},
publisher = {Cell Press},
reportid = {DKFZ-2025-02508},
pages = {101918},
year = {2025},
note = {#DKFZ-MOST-Ca219#},
abstract = {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.},
keywords = {Humans / Nucleosomes: metabolism / Glioma: blood / Glioma:
genetics / Glioma: diagnosis / Glioma: pathology / Histones:
genetics / Histones: blood / Histones: metabolism / Brain
Neoplasms: blood / Brain Neoplasms: genetics / Brain
Neoplasms: diagnosis / Biomarkers, Tumor: blood /
Biomarkers, Tumor: genetics / Male / Female / Circulating
Tumor DNA: blood / Tumor Suppressor Protein p53: blood /
Tumor Suppressor Protein p53: genetics / Single Molecule
Imaging: methods / Adult / Middle Aged / DIPG (Other) /
H3-K27M (Other) / TP53 (Other) / liquid-biopsy (Other) /
oncohistones (Other) / single-molecule (Other) / Nucleosomes
(NLM Chemicals) / Histones (NLM Chemicals) / Biomarkers,
Tumor (NLM Chemicals) / Circulating Tumor DNA (NLM
Chemicals) / Tumor Suppressor Protein p53 (NLM Chemicals)},
ddc = {610},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39809263},
pmc = {pmc:PMC11866549},
doi = {10.1016/j.xcrm.2024.101918},
url = {https://inrepo02.dkfz.de/record/306282},
}