GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320565/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320565GEOGSEfalseGenetic and pharmacologic disruption of N-Myc suppresses basal cell carcinoma [RNA-seq]Driver mutations that activate upstream Hedgehog (Hh) signaling are well-known to promote basal cell carcinoma (BCC); however, the role of recurrent secondary mutations, such as MYCN amplification, is less well understood. Here, we performed spatial transcriptomics to show that nascent murine BCC-like tumors are comprised of two tumor sub-populations that differ in expression of Hh, stem cell and differentiation markers. Using a newly developed cell culture formulation termed “RRi conditions,” we established several mouse BCC cell lines, identify novel genes associated with Hh pathway activation (Wnt7b, Tgfb3, Cxcl14), and show that inducible N-MYC expression suppresses Notch signaling and Krt10, a canonical squamous differentiation marker. Furthermore, we report that genetically ablating N-Myc slows tumor initiation and progression, and that an immunomodulatory drug, imiquimod, can suppress N-Myc and regress nascent lesions. Altogether, our findings demonstrate that BCCs upregulate N-MYC to counteract differentiation, and support the use of imiquimod to restrict tumor progression.2026/09/12GSE320565GSM9545792GSM9545793GSM9545790GSM9545791GSM9545796GSM9545797GSM9545794GSM9545795GSM9545789GSM9545800GSM9545801GSM9545787GSM9545798GSM9545799GSM9545788GSM9545810GSM9545804GSM9545805GSM9545802GSM9545803GSM9545808GSM9545809GSM9545806GSM954580724247320565Mus musculus