Mass Spectrometry-Based Profiling of Histone Post-Translational Modifications in Uveal Melanoma Tissues, Human Melanocytes, and Uveal Melanoma Cell Lines - A Pilot Study
- Martina C Herwig-Carl 1,2,3, Amit Sharma 1,4, Verena Tischler 5, Natalie Pelusi 5, Karin U Loeffler 1,2, Frank G Holz 1,3, Michael Zeschnigk 6, Solange Landreville 7, Claudia Auw-Haedrich 8, Roberta Noberini 9, Tiziana Bonaldi 9,10
- Martina C Herwig-Carl 1,2,3, Amit Sharma 1,4, Verena Tischler 5
- 1Department of Ophthalmology, University Hospital Bonn, Bonn, Germany.
- 2Division of Ophthalmic Pathology, University Hospital Bonn, Bonn, Germany.
- 3Centrum for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Germany.
- 4Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.
- 5Institute of Pathology, University Hospital Bonn, Bonn, Germany.
- 6Institute of Human Genetics, University Hospital Essen, Essen, Germany.
- 7Department of Ophthalmology and Otolaryngology-Cervicofacial Surgery, Université Laval, Quebec City, Quebec, Canada.
- 8Department of Ophthalmology, University Hospital Freiburg, Freiburg, Germany.
- 9Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy.
- 10Department of Oncology and Haematology-Oncology (DIPO), University of Milan, Milan, Italy.
- 0Department of Ophthalmology, University Hospital Bonn, Bonn, Germany.
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View abstract on PubMed
Summary
This summary is machine-generated.Epigenetic alterations in uveal melanoma (UM) involve distinct histone post-translational modification (PTM) patterns. These patterns may aid in UM diagnosis and prognosis, with specific cell lines proving useful for further study.
Area Of Science
- Oncology
- Epigenetics
- Ophthalmology
Background
- Uveal melanoma (UM) pathogenesis is not fully understood, particularly regarding epigenetic alterations.
- Histone post-translational modifications (PTMs) are key epigenetic regulators of gene expression and chromatin accessibility.
- Characterizing epigenetic features in UM is crucial for understanding disease mechanisms and identifying prognostic markers.
Purpose Of The Study
- To investigate the role of histone PTMs in the pathogenesis of UM.
- To explore the potential prognostic relevance of epigenetic alterations in UM.
- To comprehensively profile histone PTMs in UM tissues and cell lines.
Main Methods
- Analysis of formalin-fixed paraffin-embedded (FFPE) UM tissues (n=24) and control samples (n=12).
- Quantitative liquid chromatography-mass spectrometry (LC-MS) was used to profile histone PTMs.
- Epigenetic profiling was also performed on UM cell lines (n=7) and melanocytes (n=8).
Main Results
- Hierarchical clustering revealed significant differences in histone PTMs between UM and normal samples.
- Specific histone modifications, including acetylations and H4K20me1, were altered in BAP1 and GNA11/GNAQ mutant UM.
- UM cell lines MP65 and UPMM1 exhibited histone PTM patterns closely resembling primary UM tissues.
Conclusions
- Distinct histone PTM patterns exist in UM, suggesting potential diagnostic and prognostic value.
- Further validation in larger cohorts is necessary to confirm these epigenetic findings.
- The study identified suitable UM cell line models for future epigenetic research.
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