Differential gene set enrichment of the epithelial-mesenchymal transition pathway in BRAF- vs. NRAS-mutated metastatic melanoma.

Abstract

Melanoma is a leading cause of cancer-related deaths and is frequently driven by mutations in the BRAF and NRAS genes. These mutations disrupt key cellular signalling pathways that promote tumour growth and metastasis, but they have distinct biological and clinical implications, particularly in their response to treatment and impact on patient prognosis. The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells undergo changes in response to specific transcription factors. There are currently few studies investigating the EMT within BRAF and NRAS mutations. The aim of this study was to further elucidate activation of the EMT pathway in metastatic melanoma, focusing on BRAF- and NRAS-mutated samples from The Cancer Genome Atlas. Gene Set Enrichment Analysis revealed that BRAF mutations were more significantly associated with increased EMT activation relative to all other mutations in the dataset. In contrast, NRAS mutations were not significantly associated with gene expression of the EMT pathway, suggesting alternative mechanisms for metastasis.