The immune response-related genomic alterations in patients with malignant melanoma

Area of Science:

• Oncology
• Genomics
• Immunotherapy

Background:

• Immune checkpoint inhibitors (ICIs) improve survival in advanced melanoma.
• Patient response to ICIs varies, necessitating predictive biomarkers.
• Tumor genomic profiling may enhance treatment prediction.

Purpose of the Study:

• To investigate if tumor genomic profiling predicts clinical benefit from ICIs in melanoma patients.
• To identify specific gene mutations associated with treatment response.

Main Methods:

• Integrated next-generation sequencing (NGS) data with clinicopathologic characteristics.
• Analyzed mutational profiles, including BRAF/RAS/NF1 status and mutational signatures.
• Correlated gene mutations and PD-L1 expression with progression-free survival (PFS) and durable clinical benefit (DCB).

Main Results:

• Identified known immunotherapy-related genes with high mutation frequency.
• Found 43.2% of patients had BRAF/RAS/NF1 mutations; 56.8% were Triple-WT.
• Mutational signature 6 (DNA mismatch repair deficiency) was observed.
• Higher PD-L1 expression (≥1%) correlated with improved PFS but not DCB.
• FAT1, ATM, BRCA2, LRP1B, and PBRM1 mutations were frequent in patients with DCB, independent of PD-L1 status.

Conclusions:

• Tumor genomic profiling offers insights into melanoma patient response to ICIs.
• Specific gene mutations (FAT1, ATM, BRCA2, LRP1B, PBRM1) may serve as predictive biomarkers for ICIs efficacy.
• Further research into these molecular signatures can guide personalized melanoma treatment strategies.