Fusion of the ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X;22‐translocation. Issue 7 (12th April 2013)

• Record Type: Journal Article
• Authors: Panagopoulos, Ioannis; Thorsen, Jim; Gorunova, Ludmila; Haugom, Lisbeth; Bjerkehagen, Bodil; Davidson, Ben; Heim, Sverre; Micci, Francesca
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 7(2013:Jul.)
• Page Start: 610
• Page End: 618
• Publication Date: 2013-04-12
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22057
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Endometrial stromal sarcomas (ESS) are genetically heterogeneous uterine tumors in which a <italic>JAZF1‐SUZ12</italic> chimeric gene resulting from the chromosomal translocation t(7;17)(p15;q21) as well as <italic>PHF1</italic> rearrangements (in chromosomal band 6p21) with formation of <italic>JAZF1‐PHF1</italic>, <italic>EPC1‐PHF1</italic>, and <italic>MEAF6‐PHF1</italic> chimeras have been described. Here, we investigated two ESS characterized cytogenetically by the presence of a der(22)t(X;22)(p11;q13). Whole transcriptome sequencing one of the tumors identified a <italic>ZC3H7‐BCOR</italic> chimeric transcript. Reverse transciptase‐PCR with the <italic>ZC3H7B</italic> forward and <italic>BCOR</italic> reverse primer combinations confirmed the presence of a <italic>ZC3H7‐BCOR</italic> chimeric transcript in both ESS carrying a der(22)t(X;22) but not in a control ESS with t(1;6) and the <italic>MEAF6‐PHF1</italic> fusion. Sequencing of the amplified cDNA fragments showed that in both cases ESS exon 10 of <italic>ZC3H7B</italic> (from 22q13; accession number NM_017590 version 4) was fused to exon 8 of <italic>BCOR</italic> (from Xp11; accession number NM_001123385 version 1). Reciprocal multiple <italic>BCOR‐ZC3H7B</italic> cDNA fragments were amplified in only one case suggesting that <italic>ZC3H7B‐BCOR</italic>, on the der(22)t(X;22), is the pathogenetically important fusion gene. The putative ZC3H7B‐BCOR protein would contain the tetratricopeptide repeats and LD motif from ZC3H7B and the AF9 binding site (1093‐1233aa), the 3 ankyrin repeats (1410‐1509 aa), and the NSPC1 binding site of BCOR. Although the presence of these motifs suggests various functions of the chimeric protein, it is possible that its most important role may be in epigenetic regulation. Whether or not the (patho)genetic subsets <italic>JAZF1‐SUZ12</italic>, <italic>PHF1</italic> rearrangements, and <italic>ZC3H7B‐BCOR</italic> correspond to any phenotypic, let alone clinically important, differences in ESS remain unknown. © 2013 Wiley Periodicals, Inc.</p> </abstract>