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Human Molecular Genetics Advance Access originally published online on May 25, 2005
Human Molecular Genetics 2005 14(14):1955-1963; doi:10.1093/hmg/ddi200
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Fusion of the SUMO/Sentrin-specific protease 1 gene SENP1 and the embryonic polarity-related mesoderm development gene MESDC2 in a patient with an infantile teratoma and a constitutional t(12;15)(q13;q25)

Imke M. Veltman1, Lilian A. Vreede1, Jinke Cheng2, Leendert H.J. Looijenga3, Bert Janssen1, Eric F.P.M. Schoenmakers1, Edward T.H. Yeh2 and Ad Geurts van Kessel1,*

1Department of Human Genetics, 417 Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands, 2Department of Cardiology, Unit 449, University of Texas—MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA and 3Department of Pathology, Erasmus Medical Center/Daniel den Hoed, PO Box 1738, 3000 DR Rotterdam, The Netherlands

* To whom correspondence should be addressed. Tel: +31 243614107; Fax: +31 243540488; Email: a.geurtsvankessel{at}antrg.umcn.nl

Received February 4, 2005; Revised April 10, 2005; Accepted May 17, 2005

Recently, we identified a patient with an infantile sacrococcygeal teratoma and a constitutional t(12;15)(q13;q25). Here, we show that, as a result of this chromosomal translocation, the SUMO/Sentrin-specific protease 1 gene (SENP1) on chromosome 12 and the embryonic polarity-related mesoderm development gene (MESDC2) on chromosome 15 are disrupted and fused. Both reciprocal SENP1–MESDC2 (SEME) and MESDC2–SENP1 (MESE) fusion genes are transcribed in tumor-derived cells and their open reading frames encode aberrant proteins. As a consequence of this, and in contrast to wild-type (WT) MESDC2, the translocation-associated SEME protein is no longer targeted to the endoplasmatic reticulum, leading to a presumed loss-of-function as a chaperone for the WNT co-receptors LRP5 and/or LRP6. Ultimately, this might lead to abnormal development and/or routing of germ cell tumor precursor cells. SUMO, a post-translational modifier, plays an important role in several cellular key processes and is cleaved from its substrates by WT SENP1. Using a PML desumoylation assay, we found that translocation-associated MESE proteins exhibit desumoylation capacities similar to those observed for WT SENP1. We speculate that spatio-temporal disturbances in desumoylating activities during critical stages of embryonic development might have predisposed the patient. Together, the constitutional t(12;15)(q13;q25) translocation revealed two novel candidate genes for neonatal/infantile GCT development: MESDC2 and SENP1.


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 GENES CELLSHome page
T. Kuwata and T. Nakamura
BCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear body
Genes Cells, September 1, 2008; 13(9): 931 - 940.
[Abstract] [Full Text] [PDF]


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