Fusion of the ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X;22-translocation
Version of Record online: 12 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Genes, Chromosomes and Cancer
Volume 52, Issue 7, pages 610–618, July 2013
How to Cite
Panagopoulos, I., Thorsen, J., Gorunova, L., Haugom, L., Bjerkehagen, B., Davidson, B., Heim, S. and Micci, F. (2013), Fusion of the ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X;22-translocation. Genes Chromosom. Cancer, 52: 610–618. doi: 10.1002/gcc.22057
- Issue online: 15 MAY 2013
- Version of Record online: 12 APR 2013
- Manuscript Accepted: 14 FEB 2013
- Manuscript Received: 22 JAN 2013
- The Norwegian Cancer Society, Helse Sør-Øst, and Centre for Cancer Biomedicine
Endometrial stromal sarcomas (ESS) are genetically heterogeneous uterine tumors in which a JAZF1-SUZ12 chimeric gene resulting from the chromosomal translocation t(7;17)(p15;q21) as well as PHF1 rearrangements (in chromosomal band 6p21) with formation of JAZF1-PHF1, EPC1-PHF1, and MEAF6-PHF1 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 ZC3H7-BCOR chimeric transcript. Reverse transciptase-PCR with the ZC3H7B forward and BCOR reverse primer combinations confirmed the presence of a ZC3H7-BCOR chimeric transcript in both ESS carrying a der(22)t(X;22) but not in a control ESS with t(1;6) and the MEAF6-PHF1 fusion. Sequencing of the amplified cDNA fragments showed that in both cases ESS exon 10 of ZC3H7B (from 22q13; accession number NM_017590 version 4) was fused to exon 8 of BCOR (from Xp11; accession number NM_001123385 version 1). Reciprocal multiple BCOR-ZC3H7B cDNA fragments were amplified in only one case suggesting that ZC3H7B-BCOR, 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 JAZF1-SUZ12, PHF1 rearrangements, and ZC3H7B-BCOR correspond to any phenotypic, let alone clinically important, differences in ESS remain unknown. © 2013 Wiley Periodicals, Inc.