WT1 is a DNA Binding Protein Containing Four C2H2 Zinc Fingers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 The DNA Binding Domain ofWT1 **********************************************~*** 90 WT1 Inhibits Tag and SV40 Origin Dependent Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 WT1 is an Unusual C2H2 Zinc Finger Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 WT1 is a Transcriptional Regulator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Possible Downstream Targets ofWT1 Transcriptional Regulation . . . 103 Protein-Protein Interactions Involving WT1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 Other Factors that May Contribute to or Modify the Cellular Function ofWT1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 WT1 and Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 7. Naturally Occurring Mutations in the WTJ Gene . . . . . . . . . . . . . . . . . . 113 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 WTI Mutations in Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Analysis of WTI Mutations in Tumors Other than Wilms Tumor . . . 122 Constitutional WTI Mutations and the Denys-Drash Syndrome . . . . . . 125 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 8. Other Loci Implicated in Wtlms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Nephrogenic Rests, WTI Mutations and Wilms Tumor . . . . . . . . . . . . . . . . . . . 137 Undetectable WTI Mutations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Wilms Tumor and WITI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Loss of Heterozygosity for Chromosome 1 p and 16q . . . . . . . . . . . . . . . . . . . . . . . . 141 Wilms Tumor and Beckwith-Wiedemann Syndrome . . . . . . . . . . . . . . . . . . . . . . . . 141 Wilms Tumor and Perlman Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 Imprinting, IGF/l, HI9 and Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 Wilms Tumor and Li-F raumeni Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Familial Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Wilms Tumor and Other Disease Associations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 7 =====PREFACE===== ilms tumor is a common pediatric neoplasm of the kidney which has been W considered a paradigm for understanding the etiology of embryonal tu mors.

Together with Consulting Editor Dr. Bonita Stanton, Guest Editors Dr. Max Coppes and Leontein Kremer have put together a comprehensive monograph that updates pediatricians on pediatric cancer survivorship. They have selected worldwide experts who have contributed the most current clinical reviews to provide the information you need for care of the pediatric cancer patient. Articles are devoted specifically to the following topics: Stories from survivors and introduction to survivorship; What we know about survivors and how we know this: Early studies, early cohorts, registries and current cohorts of survivors; Radiotherapy and late effects; Guidelines for survivorship care after childhood cancer; Lifestyle, fatigue, social integration in survivors; Psychological & neurocognitive health; Second cancer risk: Risk, exposures, genetics; Cardiovascular (including genetics ) and pulmonary disease; Fertility and reproductive complications; Endocrine health conditions, including thyroid, growth, bone, and metabolic syndrome; Renal and hepatic health after childhood cancer; Hearing and other neurologic problems; and The future of survivorship (future challenges and research) including new agents. Pediatricians will come away with the information they need to improve patient outcomes.

Dr. Coppes and his co-Editors have created a comprehensive table of contents that addresses the full spectrum of food allergies in children. Articles are presented to be most useful to pediatricians, as the issue begins with the clinical presentation and epidemiology of food allergy, and then progresses to the diagnostic testing and pahthophysiology.? Articles are also included that are devoted to specific types of food allergy, dairy, soy, egg, peanut, and tree nut. Finally, articles are also devoted to living with food allergies, management of allergies in schools and camps, and therapies for food allergies.

The subject of Pediatric Bone Marrow Transplantation is reviewed in this issue of Pediatric Clinics. Guest Editors Drs. Max Coppes, Terry Fry, and Crystal Mackall have assembled a panel of experts who offer reviews on topics including Allogeneic BMT for leukemia, GVL in pediatric leukemia, Stem cell source and outcome following BMT in children, Acute GVHD in children, Chronic GVHD in children, BMT for Hemoglobinopathies, BMT for immunodeficiency, BMT for rheumatologic disorders and other benign diseases, Autologous and Allogeneic BMT for solid tumors, Late effects following BMT, Cell therapies/vaccines for malignancy and infections, BMT for metabolic disorders, BMT for bone marrow failure syndromes, and Immunotherapy in the context of SCT.

With collaboration of Dr. Bonita Stanton, Drs. Coppes and Fisher-Owens have created a current issue that looks at oral health in children, with a much needed update in the literature for pediatricians. Top experts have contributed clinical reviews on the following topics: Oral Health and Development; Infant Oral Health and the Influence of Habits; Prevention of tooth decay; Fluoride; Caries; Disparities in Children's Oral Health (including Oral Health of Native Children); Children with Special Health Care Needs; Orthodontics; Oral Manifestations of Systemic Disease (specific to pediatrics and life course); Soft Tissue; Trauma; The Role of Primary Care Physicians (pediatricians and others) in Prevention Oral Disease; and Oral Health Care/Policies. Pediatricians will come away with the current clinical recommendations they need to improve oral health in children.