Evaluating Gene Fusions as Prognostic Biomarkers and Therapeutic Targets in Immune Checkpoint Blockade-Treated Advanced Melanoma: A Retrospective Analysis.

ABSTRACT: Advanced melanoma, characterized by its aggressiveness and genomic complexity, demands improved prognostic and therapeutic strategies, particularly for patients with limited response to immune checkpoint blockade (ICB). Gene fusions, proposed as enhancers of tumor immunogenicity through neoantigens, also reflect chromosomal instability, which influences tumor evolution and therapy outcomes. However, their impact on melanoma remains unexplored. By retrospectively analyzing baseline tumors from 222 ICB-treated patients, we found a high tumor fusion burden (TFB-H) correlation with poor RECIST response, reduced overall survival (time-dependent ROC > 0.6, P << 0.01), and increased mortality risk (HR = 2, P < 0.01). TFB-H was found to be strongly associated with chromosomal instability (β = 0.72

SUBMITTER: Nibeyro G 

PROVIDER: S-EPMC12344778 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature