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H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications
by
Giuseppe Angelico
Giuseppe Angelico 1,†,
Manuel Mazzucchelli
Manuel Mazzucchelli 2,†,
Giulio Attanasio
Giulio Attanasio 2,
Giordana Tinnirello
Giordana Tinnirello 2,
Jessica Farina
Jessica Farina 2,
Magda Zanelli
Magda Zanelli 3,
Andrea Palicelli
Andrea Palicelli 3,
Alessandra Bisagni
Alessandra Bisagni 3,
Giuseppe Maria Vincenzo Barbagallo
Giuseppe Maria Vincenzo Barbagallo 4,
Francesco Certo
Francesco Certo 4,
Maurizio Zizzo
Maurizio Zizzo 5,
Nektarios Koufopoulos
Nektarios Koufopoulos 6,
Gaetano Magro
Gaetano Magro 2,
Rosario Caltabiano
Rosario Caltabiano 2 and
Giuseppe Broggi
Giuseppe Broggi 2,*
1
Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy
2
Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, Anatomic Pathology, University of Catania, 95123 Catania, Italy
3
Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
4
Department of Neurological Surgery, Policlinico “G. Rodolico-S. Marco” University Hospital, 95121 Catania, Italy
5
Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
6
Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2024, 16(20), 3451; https://doi.org/10.3390/cancers16203451 (registering DOI)
Submission received: 9 September 2024
/
Revised: 8 October 2024
/
Accepted: 10 October 2024
/
Published: 11 October 2024
Simple Summary
This article herein presented explores the role of the epigenetic marker H3K27me3 in tumors of the Central Nervous System, highlighting its importance for diagnosis, prognosis, and treatment. H3K27me3 involves the trimethylation of lysine 27 on the histone H3 protein, which is essential for regulating gene activity and maintaining chromatin structure. A reduction in H3K27me3 levels is commonly seen in CNS tumors such as diffuse midline gliomas and meningiomas and is associated with more aggressive tumor behavior and a worse prognosis. This article emphasizes the utility of H3K27me3 loss in tumor diagnosis, prognosis, and the advancement of targeted therapies.
Abstract
Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.g., in X-chromosome inactivation). Notably, a reduction in H3K27me3 levels, frequently tied to mutations in the H3 gene family such as H3F3A and HIST1H3B, is evident in diverse brain tumor variants, including the diffuse midline glioma characterized by the H3K27M mutation and certain pediatric high-grade gliomas. The loss of H3K27me3 has been linked to more aggressive behavior in meningiomas, with the trimethylation loss associated with significantly shorter recurrence-free survival (RFS) among grade 2 meningiomas, albeit not within grade 1 tumors. Pediatric posterior fossa ependymomas characterized by a lowered H3K27me3 and DNA hypomethylation exhibit poor prognosis, underscoring the prognostic significance of these epigenetic alterations in CNS tumors. Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology.
Share and Cite
MDPI and ACS Style
Angelico, G.; Mazzucchelli, M.; Attanasio, G.; Tinnirello, G.; Farina, J.; Zanelli, M.; Palicelli, A.; Bisagni, A.; Barbagallo, G.M.V.; Certo, F.;
et al. H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications. Cancers 2024, 16, 3451.
https://doi.org/10.3390/cancers16203451
AMA Style
Angelico G, Mazzucchelli M, Attanasio G, Tinnirello G, Farina J, Zanelli M, Palicelli A, Bisagni A, Barbagallo GMV, Certo F,
et al. H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications. Cancers. 2024; 16(20):3451.
https://doi.org/10.3390/cancers16203451
Chicago/Turabian Style
Angelico, Giuseppe, Manuel Mazzucchelli, Giulio Attanasio, Giordana Tinnirello, Jessica Farina, Magda Zanelli, Andrea Palicelli, Alessandra Bisagni, Giuseppe Maria Vincenzo Barbagallo, Francesco Certo,
and et al. 2024. "H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications" Cancers 16, no. 20: 3451.
https://doi.org/10.3390/cancers16203451
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