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)
Open Access
- 25 May 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 14 (14), 1955-1963
- https://doi.org/10.1093/hmg/ddi200
Abstract
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.Keywords
This publication has 59 references indexed in Scilit:
- Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1Biochemical Journal, 2005
- Constitutional t(5;7)(q11;p15) rearranged to acquire monosomy7q and trisomy 1q in a patient with myelodysplastic syndrome transforming to acute myelocytic leukemiaCancer Genetics and Cytogenetics, 2004
- SUMO: a regulator of gene expression and genome integrityOncogene, 2004
- Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 and 25 differentlyJournal of Cell Science, 2003
- Localisation of susceptibility genes for familial testicular germ cell tumourAPMIS, 2003
- Deletion mapping of 6q21-26 and frequency of 1p36 deletion in childhood endodermal sinus tumors by microsatellite analysisOncogene, 2001
- Identification of Mesoderm Development (mesd) Candidate Genes by Comparative Mapping and Genome Sequence AnalysisGenomics, 2001
- Localization to Xq27 of a susceptibility gene for testicular germ-cell tumoursNature Genetics, 2000
- Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteinsOncogene, 2000
- Pathogenesis of testicular germ cell tumoursReviews of Reproduction, 1999