title: RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12).
abstract: 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.
authors: Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ioannis.panagopoulos@rr-research.no
authors: Ioannis
authors: I
authors: Panagopoulos
authors: Jim
authors: J
authors: Thorsen
authors: Ludmila
authors: L
authors: Gorunova
authors: Francesca
authors: F
authors: Micci
authors: Lisbeth
authors: L
authors: Haugom
authors: Ben
authors: B
authors: Davidson
authors: Sverre
authors: S
authors: Heim
mesh_terms: D000328:Adult; D000368:Aged; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000302:isolation & purification; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification; D017423:Sequence Analysis, RNA; D014178:Translocation, Genetic; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human