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Wilms Tumor as a Model for Cancer Biology

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Wilms’ tumor of the kidney (WT) is the most common solid tumor of childhood, and it was first described in detail by Max Wilms’ in 1899. WT is a paradigm of childhood cancer, because it has served as a model from four distinct perspectives. First, it was one of three tumors used by Knudson in the early 1970s as a model for understanding the epidemiology of childhood cancer. Second, WT has played a key role is the molecular biology of childhood cancer. WT was one of the first examples in which a tumor suppressor gene was mapped by somatic genetic alterations in the tumors, compared to normal tissues, i.e., somatic cell gene mapping. Third, WT was the tumor in which abnormal imprinting in cancer was discovered. As such, it has been a model for epigenetic alterations in cancer. Finally, WT is a model for understanding the pathology of childhood cancer. Pediatric solid tumors, unlike adult malignancies, typically reflect normal developmental stages of organogenesis. As such, Wilms’ tumor has served as a developmental paradigm for nephrogenesis. The purpose of this chapter is to describe the evolution of WT as a model for cancer from each of these perspectives, and then to synthesize them in a unifying view that hopefully provides novel insights into the mechanism of cancer in general.
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