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Abnormal RNA expression of 11p15 imprinted genes and kidney developmental genes in Wilms' tumor
C Schwienbacher1, A Angioni, R Scelfo
1Department of Experimental and Diagnostic Medicine, Interdepartment Center for Biotechnology, University of Ferrara, Italy.
Abstract:
Wilms' tumor (WT) is caused by abnormal development of embryonal kidney cells. WT cells are frequently affected by deletions or functional inactivation of maternal alleles at chromosome 11p15, which indicates that the loss of maternally expressed genes in this region plays an important role in WT pathogenesis. Maternally expressed genes indeed exist within an imprinted region at 11p15.5. Among these, BWR1C is highly expressed in fetal but not in adult kidney, which suggests that it may fulfil an important role in kidney development. Here, we demonstrate that the lack of BWR1C expression is common in WT. Its homology with the proapoptotic gene TDAG51 suggests that the loss of BWR1C expression may be relevant in WT development. In addition, the analysis of the expression of other 11p15 imprinted genes and kidney-developmentally regulated genes indicates that IGF2 overexpression, inappropriate coexpression of RET and GDNF and, in some cases, down-regulation of CDKN1C may also play an important role in the pathogenesis of WT. Our results add new elements to the understanding of the biological basis of WT, which may have implications for WT diagnosis and therapy.
Insights
Loss of BWR1C expression is common in Wilms tumor (WT), a childhood kidney cancer. This finding, along with other genetic alterations, deepens our understanding of WT development and potential therapies.
Area of Science:
- Genetics
- Developmental Biology
- Oncology
Background:
- Wilms tumor (WT) arises from abnormal fetal kidney cell development.
- Genetic alterations in chromosome 11p15, particularly loss of maternally expressed genes, are implicated in WT pathogenesis.
- The imprinted gene BWR1C is highly expressed in fetal kidneys, suggesting a role in development.
Purpose of the Study:
- To investigate the role of BWR1C expression in Wilms tumor.
- To explore the involvement of other imprinted and kidney development genes in WT pathogenesis.
- To enhance understanding of WT's biological basis for improved diagnosis and therapy.
Main Methods:
- Analysis of BWR1C expression in Wilms tumor samples.
- Examination of other 11p15 imprinted genes and kidney development-related genes.
- Comparative gene expression profiling.
Main Results:
- Lack of BWR1C expression is frequently observed in Wilms tumors.
- BWR1C's homology to the proapoptotic gene TDAG51 suggests a role in WT development.
- IGF2 overexpression, altered RET/GDNF coexpression, and CDKN1C downregulation are also associated with WT.
Conclusions:
- The loss of BWR1C expression is a significant factor in Wilms tumor development.
- Aberrant expression of multiple imprinted and developmental genes contributes to WT pathogenesis.
- These findings offer new insights into WT biology, potentially impacting clinical diagnosis and treatment strategies.