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Adv."],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>Inflammatory breast cancer (IBC), an aggressive and lethal breast cancer subtype, lacks unequivocal genomic differences or robust biomarkers that differentiate it from non-IBC. Here, TGIRT-seq revealed myriad differences in tumors, PBMC, and plasma RNAs that distinguished IBC patients from non-IBC patients and healthy donors across different tested breast cancer subtypes. By mapping reads to genome and transcriptome reference sequences and quantitating intron-to-exon read depth ratios (IDRs), we developed methods for parallel analysis of transcriptional and posttranscriptional gene regulation. This analysis identified numerous protein-coding genes in IBC patient tumors and PBMCs with high IDRs, suggesting rate-limiting RNA splicing that decreases mRNA production. Mirroring gene expression differences in tumors and PBMCs, overrepresented protein-coding gene RNAs in IBC patient plasma were largely intron RNA fragments, while those in non-IBC patient and healthy donor plasma were largely mRNA fragments. Our findings provide insights into IBC and should enable monitoring disease progression by liquid biopsy.<\/jats:p>","DOI":"10.1126\/sciadv.adu0031","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:59:01Z","timestamp":1777658341000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Pervasive enhanced transcription in inflammatory breast cancer tumors and PBMCs impacts RNA splicing and intronic RNAs in plasma"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-3549","authenticated-orcid":true,"given":"Dennis","family":"Wylie","sequence":"first","affiliation":[{"name":"Departments of Molecular Biosciences and Medicine \/ Oncology, University of Texas at Austin, Austin, TX 78712, 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