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Updated: May 16, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Genomics of Primary and Metastatic Cutaneous Melanoma: A Systematic Review and Meta-Analysis
Manh Duc Hoang1,2, Thi Oanh Bui1,2, Van Tu Dao1,2
1National Cancer Hospital, Cancer Research and Clinical Trials Center, Hanoi, Vietnam.
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:
We aimed 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 to assess the prevalence of gene mutations and copy number alterations. Relevant studies were identified in MEDLINE and Embase up to October 2024 using the search algorithm ((Mutation) OR "Genomics"[Mesh]) AND ("Melanoma"[Mesh]). Data were synthesized using random-effects meta-analyses to estimate the pooled prevalence of gene mutations and copy number variations, with heterogeneity assessed using I2 statistics. This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results:
Ninety-nine publications were included, encompassing 10,386 primary cutaneous melanoma samples and 4273 metastatic samples. The most frequently mutated genes in both settings were BRAF, TERT, TP53, NRAS, and NF1. The prevalence of BRAF, NRAS, TERT, CDKN2A, and PTEN mutations was significantly higher in metastatic lesions. NRAS mutations were more common in central nervous system metastases than in other metastatic sites. In contrast, KIT mutations were more common in primary tumors. Acral melanoma exhibited a distinct molecular profile, with an overall lower mutation prevalence, particularly involving BRAF. Chromosomal losses at 9p21.3 and 9p21 were commonly observed in both primary and metastatic tumors, with higher prevalence in primary tumors.
Conclusions:
Our findings highlight distinct genomic differences between primary and metastatic melanoma, underscoring the value of metastatic tumor biopsies in informing molecularly guided treatment decisions.
Insights
Genomic analysis reveals key differences between primary and metastatic melanoma. Understanding these alterations, particularly in BRAF and NRAS mutations, can guide more effective melanoma treatment strategies.
Area of Science:
- Oncology
- Genomics
- Dermatology
Background:
- Melanoma is an aggressive skin cancer with limited treatment responses.
- Genomic characterization is crucial for understanding melanoma progression and developing therapies.
Purpose of the Study:
- To characterize genomic alterations in cutaneous melanoma.
- To compare mutation prevalence between primary and metastatic tumors for improved therapeutic strategies.
Main Methods:
- Systematic review and meta-analysis of genomic data from cutaneous melanoma studies.
- Inclusion of 99 publications with 10,386 primary and 4,273 metastatic samples.
- Random-effects meta-analyses to estimate pooled prevalence of gene mutations and copy number variations.
Main Results:
- BRAF, TERT, TP53, NRAS, and NF1 were the most frequently mutated genes.
- Metastatic lesions showed higher prevalence of BRAF, NRAS, TERT, CDKN2A, and PTEN mutations.
- Distinct molecular profiles were observed in acral melanoma and specific metastatic sites (e.g., CNS).
Conclusions:
- Significant genomic differences exist between primary and metastatic melanoma.
- Metastatic tumor biopsies are valuable for guiding molecularly targeted melanoma treatments.
