Comprehensive analysis of the melanoma DNA methylome identifies LY75 methylation as an independent marker predicting poor clinical outcome
- Author
- Karin van den Hurk, Kim Lommen, Louis Coussement (UGent) , Danique van den Kerkhof, Mara Beckers, Geert Trooskens (UGent) , Leander Van Neste (UGent) , Marloes Oosterhof, Remco van Doorn, Joost J. van den Oord, Thomas Kerkhofs, Maureen J.B. Aarts, Bram Ramaekers, Manuela Joore, Véronique J.L. Winnepenninckx, Wim Van Criekinge (UGent) , William Gallagher, Tim De Meyer (UGent) , Kim M. Smits and Manon van Engeland
- Organization
- Abstract
- Accurate risk assessment of local recurrences or metastases is essential for melanoma treatment, but current clinical parameters are suboptimal. Therefore, we conducted a comprehensive DNA methylation analysis to identify prognostic markers that could improve risk prediction in patients with melanoma. We integrated methyl-binding domain sequencing, RNA sequencing, Infinium HumanMethylation450 analyses, and The Cancer Genome Atlas data to identify potential prognostic DNA methylation markers. Validation was performed using methylation-specific PCR in 2 independent melanoma cohorts as well as an in silico validation using The Cancer Genome Atlas data. Cox proportional hazards models and backward stepwise elimination determined the prognostic value of candidate markers. LY75 promoter methylation, Breslow thickness, and metastatic disease at diagnosis were significant independent predictors of recurrence-free survival. LY75 promoter methylation was also found to be an independent predictor of metastatic disease development in patients with localized stage I/II melanoma specifically. This association was confirmed in a second validation cohort and The Cancer Genome Atlas melanoma dataset. LY75 promoter methylation identifies patients at high risk of recurrences or metastases, independent of conventional prognostic parameters. This marker could help refine patient selection for sentinel node biopsies, imaging, (neo)adjuvant treatment, and closer monitoring, ultimately leading to improved clinical outcomes.
- Keywords
- Epigenetics, LY75, Melanoma, Prognostic biomarker, Promoter DNA methylation, CPG ISLAND HYPERMETHYLATION, RECEPTOR, DEC-205
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01K7ECBX3676XN4T054T4H3Y9B
- MLA
- van den Hurk, Karin, et al. “Comprehensive Analysis of the Melanoma DNA Methylome Identifies LY75 Methylation as an Independent Marker Predicting Poor Clinical Outcome.” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 146, no. 2, 2026, pp. 455-469.e5, doi:10.1016/j.jid.2025.07.010.
- APA
- van den Hurk, K., Lommen, K., Coussement, L., van den Kerkhof, D., Beckers, M., Trooskens, G., … van Engeland, M. (2026). Comprehensive analysis of the melanoma DNA methylome identifies LY75 methylation as an independent marker predicting poor clinical outcome. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 146(2), 455-469.e5. https://doi.org/10.1016/j.jid.2025.07.010
- Chicago author-date
- Hurk, Karin van den, Kim Lommen, Louis Coussement, Danique van den Kerkhof, Mara Beckers, Geert Trooskens, Leander Van Neste, et al. 2026. “Comprehensive Analysis of the Melanoma DNA Methylome Identifies LY75 Methylation as an Independent Marker Predicting Poor Clinical Outcome.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 146 (2): 455-469.e5. https://doi.org/10.1016/j.jid.2025.07.010.
- Chicago author-date (all authors)
- van den Hurk, Karin, Kim Lommen, Louis Coussement, Danique van den Kerkhof, Mara Beckers, Geert Trooskens, Leander Van Neste, Marloes Oosterhof, Remco van Doorn, Joost J. van den Oord, Thomas Kerkhofs, Maureen J.B. Aarts, Bram Ramaekers, Manuela Joore, Véronique J.L. Winnepenninckx, Wim Van Criekinge, William Gallagher, Tim De Meyer, Kim M. Smits, and Manon van Engeland. 2026. “Comprehensive Analysis of the Melanoma DNA Methylome Identifies LY75 Methylation as an Independent Marker Predicting Poor Clinical Outcome.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 146 (2): 455-469.e5. doi:10.1016/j.jid.2025.07.010.
- Vancouver
- 1.van den Hurk K, Lommen K, Coussement L, van den Kerkhof D, Beckers M, Trooskens G, et al. Comprehensive analysis of the melanoma DNA methylome identifies LY75 methylation as an independent marker predicting poor clinical outcome. JOURNAL OF INVESTIGATIVE DERMATOLOGY. 2026;146(2):455-469.e5.
- IEEE
- [1]K. van den Hurk et al., “Comprehensive analysis of the melanoma DNA methylome identifies LY75 methylation as an independent marker predicting poor clinical outcome,” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 146, no. 2, pp. 455-469.e5, 2026.
@article{01K7ECBX3676XN4T054T4H3Y9B,
abstract = {{Accurate risk assessment of local recurrences or metastases is essential for melanoma treatment, but current clinical parameters are suboptimal. Therefore, we conducted a comprehensive DNA methylation analysis to identify prognostic markers that could improve risk prediction in patients with melanoma. We integrated methyl-binding domain sequencing, RNA sequencing, Infinium HumanMethylation450 analyses, and The Cancer Genome Atlas data to identify potential prognostic DNA methylation markers. Validation was performed using methylation-specific PCR in 2 independent melanoma cohorts as well as an in silico validation using The Cancer Genome Atlas data. Cox proportional hazards models and backward stepwise elimination determined the prognostic value of candidate markers. LY75 promoter methylation, Breslow thickness, and metastatic disease at diagnosis were significant independent predictors of recurrence-free survival. LY75 promoter methylation was also found to be an independent predictor of metastatic disease development in patients with localized stage I/II melanoma specifically. This association was confirmed in a second validation cohort and The Cancer Genome Atlas melanoma dataset. LY75 promoter methylation identifies patients at high risk of recurrences or metastases, independent of conventional prognostic parameters. This marker could help refine patient selection for sentinel node biopsies, imaging, (neo)adjuvant treatment, and closer monitoring, ultimately leading to improved clinical outcomes.}},
author = {{van den Hurk, Karin and Lommen, Kim and Coussement, Louis and van den Kerkhof, Danique and Beckers, Mara and Trooskens, Geert and Van Neste, Leander and Oosterhof, Marloes and van Doorn, Remco and van den Oord, Joost J. and Kerkhofs, Thomas and Aarts, Maureen J.B. and Ramaekers, Bram and Joore, Manuela and Winnepenninckx, Véronique J.L. and Van Criekinge, Wim and Gallagher, William and De Meyer, Tim and Smits, Kim M. and van Engeland, Manon}},
issn = {{0022-202X}},
journal = {{JOURNAL OF INVESTIGATIVE DERMATOLOGY}},
keywords = {{Epigenetics,LY75,Melanoma,Prognostic biomarker,Promoter DNA methylation,CPG ISLAND HYPERMETHYLATION,RECEPTOR,DEC-205}},
language = {{eng}},
number = {{2}},
pages = {{455--469.e5}},
title = {{Comprehensive analysis of the melanoma DNA methylome identifies LY75 methylation as an independent marker predicting poor clinical outcome}},
url = {{http://doi.org/10.1016/j.jid.2025.07.010}},
volume = {{146}},
year = {{2026}},
}
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