A B-Raf V600E gene signature for melanoma predicts prognosis and reveals sensitivity to targeted therapies
Background: B-Raf V600E mutations take into account about 50 % of skin cutaneous melanoma cases, and patients with this particular mutation are responsive to BRAF inhibitors. However, aberrations in other genes within the MAPK/ERK path may cascade an identical effect as B-Raf V600E mutations, rendering individuals patients responsive to BRAF inhibitors. We rationalized that defining a signature according to B-Raf path activity might be more informative for prognosis and drug sensitivity conjecture than the usual binary indicator for example mutation status.
Methods: Within this study, we defined a b –Raf signature score using RNA-seq data from TCGA. A greater score is proven not only to predict B-Raf mutation status, but additionally predict other aberrations that may similarly activate the MAPK/ERK path, for example B-Raf amplification, RAS mutation, and EGFR amplification.
Results: We demonstrated that patients dichotomized through the median B-Raf score is SB590885 much more considerably stratified compared to other metrics of calculating B-Raf aberration, for example mutation status, gene expression, and protein expression. We shown that top B-Raf score predicts greater sensitivity to B-Raf inhibitors SB590885 and PLX4720, not surprisingly, but additionally correlated with sensitivity to drugs targeting other relevant oncogenic pathways.
Conclusion: The BRAF signature may better help guide to targeted therapy for melanoma, and the like a framework does apply with other cancers and mutations to supply more details than mutation status alone.