High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma
Abstract
1. Introduction
2. Results
2.1. Clinicopathological Characteristics
2.2. Copy-Number Variations Landscape in ALM Patient Biopsies
2.3. High CNVs in ALM Biopsies Are Associated with Worse Clinicopathological Characteristics and Prognosis
2.4. Characterization of Copy-Number Variations in ALM Cell Lines
2.5. CNVsHigh Cells Secretome Exhibits an Increased Pro-Tumor Profile
2.6. CNVsHigh Secretome Induce Tumor-Promoting Macrophages Polarization and Enhanced Immunosuppressive TAMs at the Invasive Front of CNVsHigh ALM Biopsies
3. Discussion
4. Materials and Methods
4.1. Cohort Construction and Patient Information
4.2. Patient Biopsies Collection
4.3. ALM Cell Lines
4.4. Conditioned Media (CM) Collection
4.5. DNA Extraction
4.6. Multiplex Ligation-Dependent Probe Amplification (MLPA) Procedure
4.7. Immunohistochemistry (IHC)
4.8. Human Cytokine Array
4.9. Gene Set Enrichment Analysis
4.10. Monocyte Isolation from Human Peripheral Blood
4.11. In Vitro Polarization of Macrophages
4.12. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gender | |
Male | 15 (45.5) |
Female | 18 (54.5) |
Age (years) | |
Mean (±SD) | 70.2 (±15.9) |
Median (IQR) | 75 (54–83) |
Primary tumor location | |
Hands n (%) | 8 (24.2) |
Subungual | 6 (18.2) |
Finger | 2 (6.1) |
Feet n (%) | 25 (75.8) |
Subungual | 8 (24.2) |
Sole | 11 (33.3) |
Toe | 3 (9.1) |
Lateral | 2 (6.1) |
N/A | 1 (3.0) |
Breslow thickness (mm) | |
Mean (±SD) | 4.2 (±3.9) |
Median (IQR) | 2.7 (0.89–7.9) |
Ulceration n (%) | |
Yes | 20 (60.6) |
No | 13 (39.4) |
Mitotic index n (%) | |
<1/mm2 | 6 (18.2) |
≥1/mm2 | 21 (63.6) |
N/A | 6 (18.2) |
Live status n (%) | |
Alive | 16 (48.4) |
Melanoma death | 13 (39.4) |
Other causes | 4 (12.1) |
Relapse (metastasis) n (%) | |
Yes | 12 (36.3) |
No | 18 (54.5) |
Distant metastasis at diagnosis | 3 (9.1) |
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de la Rosa, I.; Sisó, P.; Ríos, C.; Gracia, J.; Cuevas, D.; Maiques, O.; Eritja, N.; Soria, X.; Angel-Baldó, J.; Gatius, S.; et al. High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma. Int. J. Mol. Sci. 2025, 26, 4097. https://doi.org/10.3390/ijms26094097
de la Rosa I, Sisó P, Ríos C, Gracia J, Cuevas D, Maiques O, Eritja N, Soria X, Angel-Baldó J, Gatius S, et al. High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma. International Journal of Molecular Sciences. 2025; 26(9):4097. https://doi.org/10.3390/ijms26094097
Chicago/Turabian Stylede la Rosa, Inés, Pol Sisó, Christopher Ríos, Judith Gracia, Dolors Cuevas, Oscar Maiques, Núria Eritja, Xavier Soria, Joan Angel-Baldó, Sonia Gatius, and et al. 2025. "High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma" International Journal of Molecular Sciences 26, no. 9: 4097. https://doi.org/10.3390/ijms26094097
APA Stylede la Rosa, I., Sisó, P., Ríos, C., Gracia, J., Cuevas, D., Maiques, O., Eritja, N., Soria, X., Angel-Baldó, J., Gatius, S., Sanchez-Moral, L., Sarrias, M.-R., Matias-Guiu, X., Martí, R. M., & Macià, A. (2025). High Copy Number Variations Correlate with a Pro-Tumoral Microenvironment and Worse Prognosis in Acral Lentiginous Melanoma. International Journal of Molecular Sciences, 26(9), 4097. https://doi.org/10.3390/ijms26094097