This study identifies that a significant portion of mutations previously annotated as coding in melanoma are actually non-coding due to the use of non-expressed reference transcripts. Specifically, mutations in the shared promoter region of IRF3 and BCL2L12 were found to downregulate their expression, leading to decreased TP53 levels and poorer responses to immunotherapy.
Misannotated non-coding mutations in promoter regions can have functional consequences, affecting gene expression and patient response to therapy; highlights the importance of integrating RNA expression data in mutation annotation.
CRISPR-Cas9 edited Mel-ST human melanocyte cell lines with mutations in the shared IRF3/BCL2L12 promoter region, generated by genOway.
Melanoma, Non-coding mutations, Gene regulation, Immunotherapy response, Functional genomics
CRISPR-Cas9 genome editing, Promoter region targeting, Human melanocyte cell line modification
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