Characterizing isoform switching events in esophageal adenocarcinoma.

Autor:	Zhang Y; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Weh KM; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Howard CL; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Riethoven JJ; Nebraska Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.; Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588, USA., Clarke JL; Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA., Lagisetty KH; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Lin J; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Reddy RM; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Chang AC; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Beer DG; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Kresty LA; Department of Surgery, Thoracic Surgery Section, University of Michigan, Ann Arbor, MI 48109, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2022 Aug 17; Vol. 29, pp. 749-768. Date of Electronic Publication: 2022 Aug 17 (Print Publication: 2022).
DOI:	10.1016/j.omtn.2022.08.018
Abstrakt:	Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was used to detect levels of RNA transcripts and identify specific isoforms in treatment-naïve esophageal tissues ranging from premalignant Barrett's esophagus (BE), BE with low- or high-grade dysplasia (BE.LGD, BE.HGD), and EAC. Samples were stratified by histopathology and TP53 mutation status, identifying significant isoform switching events with predicted functional consequences. Comparing BE.LGD with BE.HGD, a histopathology linked to cancer progression, isoform switching events were identified in 75 genes including KRAS , RNF128, and WRAP53 . Stratification based on TP53 status increased the number of significant isoform switches to 135, suggesting switching events affect cellular functions based on TP53 mutation and tissue histopathology. Analysis of isoforms agnostic, exclusive, and shared with mutant TP53 revealed unique signatures including demethylation, lipid and retinoic acid metabolism, and glucuronidation, respectively. Nearly half of isoform switching events were identified without significant gene-level expression changes. Importantly, two TP53 -interacting isoforms, RNF128 and WRAP53 , were significantly linked to patient survival. Thus, analysis of isoform switching events may provide new insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC. Competing Interests: The authors declare no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
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