Buzova, D, Petrilli, LL, Frohlich, J, Tsoneva, D.K., Bianco, SD, Braghini, MR, Alisi, A, Mastronuzzi, A, Cerveny, J, Mazza, T, Vinci, M and Vinciguerra, M (2024) Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma. Molecular Diagnosis and Therapy. ISSN 1177-1062

Text Extracellular histones profiles of pediatric H3K27-altered diffuse midline glioma.pdf - Accepted Version Restricted to Repository staff only until 8 November 2025. Download (463kB)

Abstract

Background Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. Methods A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. Results We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. Conclusions In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.

Item Type:	Article
Additional Information:	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://doi.org/10.1007/s40291-024-00754-6
Uncontrolled Keywords:	1115 Pharmacology and Pharmaceutical Sciences; Oncology & Carcinogenesis; Pharmacology & Pharmacy
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Springer
SWORD Depositor:	A Symplectic
Date Deposited:	13 Dec 2024 12:41
Last Modified:	13 Dec 2024 12:45
DOI or ID number:	10.1007/s40291-024-00754-6
URI:	https://researchonline.ljmu.ac.uk/id/eprint/25030

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