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).
Fulltext:
47827.pdf
Embargo:
until further notice
Size:
215.0Kb
Format:
PDF
Description:
Publisher’s version
Publication year
2005Source
Human Molecular Genetics, 14, 14, (2005), pp. 1955-63ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Human Genetics
Biochemistry (UMC)
Journal title
Human Molecular Genetics
Volume
vol. 14
Issue
iss. 14
Page start
p. 1955
Page end
p. 63
Subject
NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 3: Translational research; UMCN 1.2: Molecular diagnosis, prognosis and monitoringAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122508]
- Faculty of Medical Sciences [90373]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.