Home > D. General pathology > Genetic and developmental anomalies > Chromosomal diseases > Constitutional translocations > t(12;15)(q13;q25)
t(12;15)(q13;q25)
Wednesday 19 January 2011
A patient with an infantile sacrococcygeal teratoma and a constitutional t(12;15)(q13;q25) has been identified.
By 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.
Translocation-associated MESE proteins exhibit desumoylation capacities similar to those observed for WT SENP1.
Spatio-temporal disturbances in desumoylating activities during critical stages of embryonic development might have predisposed the patient.
The constitutional t(12;15)(q13;q25) translocation revealed two novel candidate genes for neonatal/infantile GCT development: MESDC2 and SENP1.
References
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). Veltman IM, Vreede LA, Cheng J, Looijenga LH, Janssen B, Schoenmakers EF, Yeh ET, van Kessel AG. Hum Mol Genet. 2005 Jul 15;14(14):1955-63. PMID: 15917269
A novel case of infantile sacral teratoma and a constitutional t(12;15)(q13;q25) pat. Veltman I, van Asseldonk M, Schepens M, Stoop H, Looijenga L, Wouters C, Govaerts L, Suijkerbuijk R, van Kessel A. Cancer Genet Cytogenet. 2002 Jul 1;136(1):17-22. PMID: 12165446