## Genetic Basis of Wilms Tumor **Key Point:** WT1 gene inactivation is the most frequent genetic alteration in Wilms tumor, present in approximately 90% of sporadic cases and 100% of bilateral cases. ### WT1 Gene Characteristics - Located on chromosome 11p13 - Functions as a tumor suppressor gene - Encodes a zinc-finger transcription factor - Critical for normal urogenital development - Loss of function leads to abnormal metanephric mesenchyme differentiation ### WAGR Syndrome Association - **W**ilms tumor - **A**niridia - **G**enitourinary anomalies - **R**etardation (intellectual disability) - Results from deletion of 11p13 region including WT1 **High-Yield:** WT1 mutations account for the majority of hereditary Wilms tumor cases and are screened in at-risk families. ### Other Genetic Alterations (Less Common) | Genetic Change | Frequency | Association | | --- | --- | --- | | WT1 loss | ~90% | Sporadic and hereditary cases | | Loss of 16q | ~15% | Unfavorable histology | | MYCN amplification | Rare | More common in neuroblastoma | | BRCA1 mutation | Not associated | Breast/ovarian cancer predisposition | **Clinical Pearl:** Bilateral Wilms tumors almost always have WT1 mutations, making genetic testing essential in these cases for family counseling. 
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