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Updated: Dec 2, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine
Baptiste Louveau1,2,3, Fanélie Jouenne1,2,3, Pauline Têtu4
1Department of Pharmacology and Solid Tumor Genomics, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 1 Avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
Background:
Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies.
Objective:
The objective of this study was to present such a customized next-generation sequencing panel in melanoma.
Methods:
Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations.
Results:
Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with BRAF, NRAS, CDKN2A, CCND1, and MET as the most frequently altered genes. Among patients with BRAFV600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with RAS hotspot mutated lesions and in patients with neither BRAFV600 nor RAS hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively.
Conclusions:
Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients' clinical management.
Insights
A custom next-generation sequencing panel for melanoma identified clinically relevant genetic alterations in 87.4% of tumors. This tailored approach aids in guiding melanoma treatment strategies and overcoming drug resistance.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Accurate tumor molecular profiling is essential for effective clinical management.
- Pan-cancer next-generation sequencing (NGS) panels offer broad molecular characterization.
- Treatment resistance and emerging drug targets necessitate tumor-specific customized panels for guiding therapy.
Purpose of the Study:
- To present a customized next-generation sequencing (NGS) panel specifically designed for melanoma.
- To demonstrate the utility of a tailored NGS panel in identifying actionable mutations in melanoma patients.
Main Methods:
- Somatic molecular profiling was performed on melanoma patients within routine care.
- High-throughput sequencing utilized a melanoma-tailored NGS panel targeting 64 genes.
- Analysis screened for single nucleotide variants (SNVs) and copy number variations (CNVs), identifying clinically relevant alterations.
Main Results:
- Analysis of 421 melanoma cases revealed at least one genetic alteration in 87.4% of lesions.
- BRAF, NRAS, CDKN2A, CCND1, and MET were the most frequently altered genes.
- Concurrent alterations conferring resistance to targeted therapies were found in a significant proportion of patients, including those with BRAFV600 mutations (44.5%) and RAS hotspot mutations (56.9%).
Conclusions:
- A tailored NGS assay and comprehensive analysis can enhance therapeutic management for melanoma patients.
- Future implementation of updated panels and multi-omic approaches will further improve clinical outcomes.
