Comprehensive long-read transcriptome analysis uncovers alternative RNA processing feature and isoform diversity in ovarian cancer progression

Post-transcriptional processing has a crucial but still largely unresolved dynamic change and role during the malignant progression of ovarian cancer, especially due to the limited read length of widely used short-read RNA sequencing being not enough to capture the transcript diversity. Here, we performed both Iso and RNA sequencing on paired normal ovarian tissues, primary tumors, and metastatic lesions from patients with ovarian cancer. We generated a comprehensive isoform atlas containing over 41,000 full-length transcripts, including many previously unannotated isoforms with coding potential. Integrative analyses revealed extensive isoform-level remodeling across disease stages, involving alternative splicing and polyadenylation. These changes often occurred without concordant alterations at the gene level, emphasizing the importance of qualitative transcript regulation. Overall design: We collected nine tissues from three patients with high-grade serous ovarian cancer (HGSOC), including normal tissues, primary ovarian tumors, and omental metastases. These samples were sequenced using PacBio long-read and DNBSEQ-T7 RNA-seq