RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12). Issue 8 (30th April 2013)

• Record Type: Journal Article
• Authors: Panagopoulos, Ioannis; Thorsen, Jim; Gorunova, Ludmila; Micci, Francesca; Haugom, Lisbeth; Davidson, Ben; Heim, Sverre
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 8(2013:Aug.)
• Page Start: 733
• Page End: 740
• Publication Date: 2013-04-30
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22068
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>EWSR1–YY1</italic> and its reciprocal <italic>YY1–EWSR1</italic> fusion transcript. Screening 15 additional cases of mesothelioma from which we had RNA but no cytogenetic information, we identified one more tumor carrying an <italic>EWSR1–YY1</italic> fusion gene but not the reciprocal <italic>YY1–EWSR1</italic> transcript. RT‐polymerase chain reaction and sequencing showed that in both cases exon 8 of <italic>EWSR1</italic> (nucleotide 1, 139, accession number NM_013986 version 3, former exon 7 in sequence with accession number X66899) was fused to exon 2 of <italic>YY1</italic> (nucleotide 1, 160, accession number NM_003403 version 3). The <italic>EWSR1</italic> breakpoint in exon 8 in the <italic>EWSR1–YY1</italic> chimeric transcript is similar to what is found in other fusions involving <italic>EWSR1</italic>such as <italic>EWSR1–FLI1</italic>, <italic>EWSR1–DDIT3</italic>, and <italic>EWSR1–ATF1</italic>. 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 <italic>EWSR1–YY1</italic> fusion is remains uncertain) and also the first time that direct involvement of YY1 in oncogenesis has been demonstrated. © 2013 Wiley Periodicals, Inc.</p> </abstract>