PLX292146

GSE98394: Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

We set out to identify molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. Gene expression changes unequivocally discriminated benign versus malignant states, and a dual epigenetic and immune signature emerged defining this transition. We discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was discriminated by a 122-epigenetic gene signature (epigenetic cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of viral mimicry were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (immune clusters) were identified. TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of RNA transcripts may be better predictors for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cells epigenome with the immune milieu with potential for future therapeutic targeting. SOURCE: Julide,Tok,CelebiDept of Dermatology, Depts of Pathology and Oncological Sciences Mount Sinai School of Medicine