June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Mass spectrometry-based profiling of histone posttranslational modifications in human melanocytes and uveal melanoma cell lines
Author Affiliations & Notes
  • Martina C Herwig-Carl
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
    Center of Integrated Oncology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Roberta Noberini
    Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy
  • Karin U Loeffler
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Frank G Holz
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Michael Zeschnigk
    human genetics, Universitatsklinikum Essen, Essen, Nordrhein-Westfalen, Germany
  • Solange Landreville
    Ophthalmology and Otolaryngology, Universite Laval Faculte de medecine, Quebec, Quebec, Canada
  • Tiziana Bonaldi
    Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy
  • Amit Sharma
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
    Neurosurgery, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Footnotes
    Commercial Relationships   Martina Herwig-Carl Glako Smith Kline, Code C (Consultant/Contractor); Roberta Noberini None; Karin Loeffler None; Frank Holz None; Michael Zeschnigk None; Solange Landreville None; Tiziana Bonaldi None; Amit Sharma None
  • Footnotes
    Support  EPIC-XS, project number 823839, funded by the Horizon 2020 programme of the European Union
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2342 – A0011. doi:
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      Martina C Herwig-Carl, Roberta Noberini, Karin U Loeffler, Frank G Holz, Michael Zeschnigk, Solange Landreville, Tiziana Bonaldi, Amit Sharma; Mass spectrometry-based profiling of histone posttranslational modifications in human melanocytes and uveal melanoma cell lines. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2342 – A0011.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : While genetic alterations in uveal melanoma (UM) have been extensively studied, epigenetic factors of UM are still not well understood. It is also evident that UM differs significantly from skin melanoma regarding clinical behaviour, genetic profile as well as responsiveness to various therapies. However, differences between skin and uveal melanocytes are not obvious. We therefore studied histone posttranslational modifications (hPTMs) which are epigenetic mechanisms regulating gene expression. HPTMs were analyzed in different UM cell lines and healthy melanocytes (from skin and uvea) to provide a deeper insight into the pathogenesis of UM.

Methods : Human skin (n=6) and uveal melanocytes (n=2) as well as human UM cell lines (n=7) were analyzed by quantitative mass spectrometry for 52 histone modifications involved in the dynamics of active and repressive chromatin.

Results : Hierarchical clustering showed clear differences between melanocytes and UM cell lines. Uveal melanocytes showed a different hPTM pattern than skin melanocytes. With regard to the UM cell lines, those with a monosomy 3 signature (MP65 and UPMM1) were distinguishable from cell lines with a disomy 3 signature (Mel 202, 92.1, UPMD1, UPMD2). The BAP1-associated mark H3K27me3 was unaltered in melanocytes and non-specifically altered in UM cell lines.

Conclusions : Our study demonstrated different hPTM patterns between skin and uveal melanocytes which both originate initally from the same precursor of melanocytes. Since the potential neoplasms arising from these melanocytes (skin and uveal melanoma, respectively) differ in their clinical behaviour and their genetic profile, hPTM may be a step towards understanding the differences between these two melanocyte subtypes. In addition, healthy uveal melanocytes were distinct from UM cell lines which could be further subgrouped with regard to chromosome 3 status. Thus, hPTM signature may be an additional prognostic marker and further studies on human tissues are warranted.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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