Clinical Report: The CpG Island Methylator Phenotype in Cutaneous Melanoma

Overview

The CpG Island Methylator Phenotype (CIMP) identifies a subtype of cutaneous melanoma. CIMP+ tumors exhibit significant epigenetic changes and genomic instability.

Background

Cutaneous melanoma is a highly aggressive skin cancer with variable responses to treatment, particularly immune checkpoint blockade. Understanding the molecular characteristics of melanoma subtypes, such as CIMP, is crucial.

Data Highlights

Key Findings

• CIMP+ tumors are associated with older age and male sex.
• Significantly worse overall and progression-free survival in CIMP+ compared to CIMP− tumors.
• 2,510 hypermethylated promoter probes linked to reduced expression of 1,707 genes in CIMP+ tumors.
• CIMP+ tumors exhibit an immune-depleted profile with lower immune checkpoint gene expression.
• Genomic profiling shows enrichment for NRAS and ARID2 mutations in CIMP+ tumors.
• CIMP+ status is significantly enriched in non-responders to immune checkpoint blockade.

Clinical Implications

CIMP as a distinct melanoma subtype has clinical relevance.

Conclusion

CIMP represents a melanoma subtype characterized by significant epigenetic and genomic alterations.

Related Resources & Content

1. Author(s)/Org, Source, Year -- Title
2. The ASCO Post, 2025 -- New Study Identifies Potential Genes Implicated in Treatment-Resistant Melanoma
3. The ASCO Post, 2018 -- Activity of T Cells in Metastatic Melanoma Resistant to Immune Checkpoint Inhibitor Treatment
4. Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up - ScienceDirect
5. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0 | Journal for ImmunoTherapy of Cancer
6. The ASCO Post — Activity of T Cells in Metastatic Melanoma Resistant to Immune Checkpoint Inhibitor Treatment
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9. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0 | Journal for ImmunoTherapy of Cancer
10. Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047 | Journal of Clinical Oncology
11. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial - PMC
12. Molecular patterns of resistance to immune checkpoint blockade in melanoma | Nature Communications
13. Characterization of the CpG island hypermethylated phenotype (CIMP) subclass in primary melanomas - PMC
14. Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives | MDPI