The MYC oncogene is involved in the onset of various tumors including Breast Cancer (BC), and the severe Triple Negative basal-like subtype (TNBC). Recent results indicate that a MYC-driven transcriptional boost relies on adequate support from the splicing machinery, resulting in spliceosomal stress and vulnerability. At the molecular level, treatment with splicing drugs leads to apoptosis through accumulation of double-stranded RNA, triggering the anti-viral signaling pathway and the corresponding innate immune response (IIR). MYC hyper-activation affects the abundance of epitranscriptional RNA modifications, important determinants of RNA fate that are linked to cancer and favour IIR escape by altering transcripts conformation. These data suggest that specific RNA modifications are important for the onset of spliceosomal vulnerability in MYC-driven BC. My research project aims at developing innovative approaches, based on state of the art sequencing techniques and mathematical modeling, for the study of aberrant transcriptional and epitranscriptional regulation in cancer, and at using them to investigate whether and how the epitranscriptome is involved in the onset of spliceosomal vulnerability in BC.