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Science 5 September 2008:
Vol. 321. no. 5894, pp. 1357 - 1361
DOI: 10.1126/science.1156725
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Reports

A Neoplastic Gene Fusion Mimics Trans-Splicing of RNAs in Normal Human Cells

Hui Li,1 Jinglan Wang,1 Gil Mor,2 Jeffrey Sklar1*

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.

1 Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
2 Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520, USA.

* To whom correspondence should be addressed. E-mail: jeffrey.sklar{at}yale.edu

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