title: A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells.
abstract: Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor-specific products that provide tumor cells with a growth and/or survival advantage. We show that normal endometrial stromal cells contain a specific chimeric RNA joining 5' exons of the JAZF1 gene on chromosome 7p15 to 3' exons of the Polycomb group gene JJAZ1/SUZ12 on chromosome 17q11 and that this RNA is translated into JAZF1-JJAZ1, a protein with anti-apoptotic activity. The JAZF1-JJAZ1 RNA appears to arise from physiologically regulated trans-splicing between precursor messenger RNAs for JAZF1 and JJAZ1. The chimeric RNA and protein are identical to those produced from a gene fusion found in human endometrial stromal tumors. These observations suggest that certain gene fusions may be pro-neoplastic owing to constitutive expression of chimeric gene products normally generated by trans-splicing of RNAs in developing tissues.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jinglan
authors.initials: J
authors.lastname: Wang
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sklar
mesh_terms: D015687:Cell Hypoxia; D002460:Cell Line; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D003676:Deferoxamine / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000235:genetics; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005091:Exons; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008597:Menstrual Cycle; D050506:Mutant Chimeric Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology; D014176:Protein Biosynthesis; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism*; D020040:Trans-Splicing; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D050506:Mutant Chimeric Proteins; D009363:Neoplasm Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; C430461:SUZ12 protein, human; D014157:Transcription Factors; D011374:Progesterone; D003676:Deferoxamine