A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells

Science. 2008 Sep 5;321(5894):1357-61. doi: 10.1126/science.1156725.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia
  • Cell Line
  • Cell Line, Tumor
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Deferoxamine / pharmacology
  • Endometrial Neoplasms / genetics
  • Endometrium / cytology
  • Endometrium / metabolism*
  • Exons
  • Female
  • Gene Fusion*
  • Humans
  • Menstrual Cycle
  • Mutant Chimeric Proteins / genetics
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Progesterone / pharmacology
  • Protein Biosynthesis
  • RNA Precursors / genetics*
  • RNA, Messenger / genetics
  • Stromal Cells / metabolism*
  • Trans-Splicing*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Translocation, Genetic

Substances

  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • JAZF1 protein, human
  • Mutant Chimeric Proteins
  • Neoplasm Proteins
  • RNA Precursors
  • RNA, Messenger
  • SUZ12 protein, human
  • Transcription Factors
  • Progesterone
  • Deferoxamine