RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12)

Genes Chromosomes Cancer. 2013 Aug;52(8):733-40. doi: 10.1002/gcc.22068. Epub 2013 Apr 30.


Mesothelioma is a rare but very aggressive tumor derived from mesothelial cells. A number of often complex but nonrandom cytogenetic abnormalities have been found in these tumors, resulting in loss of chromosome bands 14q32 and 22q12 in more than 35% of the cases. In this study, we used RNA sequencing to search for fusion transcripts in a mesothelioma carrying a t(14;22)(q32;q12) as the sole chromosomal aberration and found an EWSR1-YY1 and its reciprocal YY1-EWSR1 fusion transcript. Screening 15 additional cases of mesothelioma from which we had RNA but no cytogenetic information, we identified one more tumor carrying an EWSR1-YY1 fusion gene but not the reciprocal YY1-EWSR1 transcript. RT-polymerase chain reaction and sequencing showed that in both cases exon 8 of EWSR1 (nucleotide 1,139, accession number NM_013986 version 3, former exon 7 in sequence with accession number X66899) was fused to exon 2 of YY1 (nucleotide 1,160, accession number NM_003403 version 3). The EWSR1 breakpoint in exon 8 in the EWSR1-YY1 chimeric transcript is similar to what is found in other fusions involving EWSR1 such as EWSR1-FLI1, EWSR1-DDIT3, and EWSR1-ATF1. The EWSR1-YY1-encoded protein is an abnormal transcription factor with the transactivation domain of EWSR1 and the DNA-binding domain of YY1. This is the first study to detect a specific fusion gene in mesothelioma (the reason how frequent the EWSR1-YY1 fusion is remains uncertain) and also the first time that direct involvement of YY1 in oncogenesis has been demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Calmodulin-Binding Proteins / genetics*
  • Calmodulin-Binding Proteins / isolation & purification
  • Chromosomes, Human, Pair 14 / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mesothelioma / genetics*
  • Mesothelioma / pathology
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / isolation & purification
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / isolation & purification
  • Sequence Analysis, RNA
  • Translocation, Genetic
  • YY1 Transcription Factor / genetics*
  • YY1 Transcription Factor / isolation & purification


  • Calmodulin-Binding Proteins
  • EWSR1 protein, human
  • Oncogene Proteins, Fusion
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • YY1 Transcription Factor
  • YY1 protein, human