WT1 and Wilms Tumor Joshua Chen

Homozygous mutant mice are embryonic lethal and fail to develop kidneys and gonads, with additional defects in the heart, diaphragm, retina, olfactory epithelium, and spleen Kreidberg, J., Sariola, H., Loring, J., Maeda, M., Pelletier, J., Houseman, D., Jaenisch, R.

WT1 encodes a developmentally regulated transcription factor Rauscher, F

There are many isoforms of WT1 protein with different DNA and protein binding specificities Hohenstein, P., Hastie, N. Red represents alternative start codons, exons, RNA editing, and splices Green represents some functional sequences that may be excluded due to these processes

WT1 gene 36 or more possible WT1 protein isoforms transcriptional up-regulation transcriptional down-regulation RNA splicing translationepigenetics growth differentiation epigenetics apoptosis

Wilms tumor is the most common childhood kidney tumor and 20% have mutations in WT1 Normal kidney Kidney with Wilm’s tumor

Nephrogenic rests are often found in these tumors and are precursors to tumor cells Keeling, J.

WT1 regulates transcription of Wnt-4, a possible explanation for the role of WT1 in Wilms tumor Sim, E., Smith, A., Szilagi, E., Rae, F., Ioannou, P., Lindsay, M., Little, M. WT1 mutation in C2A

Wnt-4 is necessary for mesenchymal differentiation and nephrogenesis +/+ or +/--/- +/+ or +/- Stark, K., Vainio, S., Vassileva, G., McMahon, A d.p.c d.p.c.

9 out of 10 Wilms tumors are successfully treated using surgery, chemotherapy, and radiation. Experimental targeted therapy includes WNT/β-Catenin Pathway Modulators. ntent/12/12/2619.long

When overexpressed as in these cancers, WT1 can also acts as an oncogene Yang, L., Han, Y., Saiz, F., Minden, M.

Summary  WT1 plays a crucial role in urogenital development  WT1 has a variety of isoforms that can act in various capacities, including acting as a transcription factor  In Wilms tumor, WT1 is a tumor suppressor that normally upregulates transcription of Wnt-4  In its absence, Wnt-4 fails to be expressed, the cells fail to differentiate, and eventually may become cancerous  In other tumors, WT1 has been shown to act as an oncogene

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