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REVIEW

Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications

Sophiette G. Hong1,2, George F. Murphy2, Christine G. Lian2,*
1 Department of Human Developmental and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2 Program in Dermatopathology, Department of Pathology, Brigham and Women’s Hospital, Mass General Brigham, Harvard Medical School, Boston, MA 02115, USA
* Corresponding Author: Christine G. Lian. Email: email
(This article belongs to the Special Issue: Advances in Skin Cancer Management: From Molecular Targets to Innovative Treatments)

Oncology Research https://doi.org/10.32604/or.2026.073894

Received 28 September 2025; Accepted 19 December 2025; Published online 20 January 2026

Abstract

Malignant melanoma (MM) is a highly aggressive skin cancer known for its rapid progression, potential for metastasis, and resistance to treatment. Despite advances in targeted therapies and immunotherapy, the prognosis for metastatic melanoma remains unfavorable. Recent research has shed light on the significance of epigenetic modifications in the pathogenesis of melanoma, revealing critical mechanisms of melanoma development and progression. Epigenetic modifications, including DNA and RNA modifications, histone modifications, chromatin remodeling, and non-coding RNA regulation, disrupt normal gene expression without modifying the DNA sequence, leading to cellular transformation, invasion, immune evasion, and therapeutic resistance. The reversible nature of epigenetic modifications opens up new opportunities for melanoma recognition and classification, as well as therapeutic applications, including the development of diagnostic and prognostic biomarkers and innovative targeted therapies aimed at restoring normal gene function and enhancing the efficacy of existing treatments. This review will focus on the multifaceted role of epigenetic dysregulation in melanoma. The future integration of epigenetic data and genomic profiling with clinical outcomes, likely facilitated by artificial intelligence (AI) algorithms, holds promise for personalized treatment strategies that are informed by precise and combinatorial diagnostic tools, ultimately improving melanoma care. The study aims to deliver a comprehensive overview of the current state of epigenetics in melanoma.

Keywords

Epigenetics; malignant melanoma; DNA/RNA modification; histone modification; chromatin remodeling

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