Genomics of Primary and Metastatic Cutaneous Melanoma: A Systematic Review and Meta-Analysis
Our findings highlight distinct genomic differences between primary and metastatic melanoma, underscoring the value of metastatic tumor biopsies in informing molecularly guided treatment decisions.
Background: Melanoma is an aggressive skin cancer with limited durable responses despite therapeutic advances. Comprehensive characterization of genomic alterations may improve understanding of disease progression and inform therapeutic strategies. Objective: To characterize genomic alterations in cutaneous melanoma and compare mutation prevalences between primary and metastatic tumors to improve therapeutic strategies. Methods: We conducted a systematic review and meta‑analysis of genomic data from primary and metastatic cutaneous melanomas using MEDLINE and Embase up to October 2024. Ninety‑nine studies were included, encompassing 10,386 primary cutaneous melanoma samples and 4,273 metastatic samples. Results: The most frequently mutated genes were BRAF, TERT, TP53, NRAS, and NF1. BRAF, NRAS, TERT, CDKN2A, and PTEN mutations were significantly higher in metastatic lesions. NRAS mutations were more common in central nervous system metastases. KIT mutations were more common in primary tumors. Acral melanoma exhibited a lower mutation prevalence, particularly involving BRAF. Chromosomal losses at 9p21.3 were common in both primary and metastatic tumors, with higher prevalence in primary tumors. Conclusions: These findings highlight distinct genomic differences between primary and metastatic melanoma, underscoring the value of metastatic tumor biopsies in informing molecularly guided treatment decisions.
Cutaneous melanoma is a highly aggressive skin cancer with rising incidence. While immunotherapy and targeted therapy have improved survival, many patients develop resistance. Understanding genomic differences between primary and metastatic tumors can identify new therapeutic targets and improve personalized treatment strategies, potentially improving outcomes for advanced melanoma patients.
Bizonyítékszint: Irányelv / elfogadott gyakorlat. Magas szintű klinikai elfogadottság.
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