1. Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq.
- Author
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Phelps HM, Al-Jadiry MF, Corbitt NM, Pierce JM, Li B, Wei Q, Flores RR, Correa H, Uccini S, Frangoul H, Alsaadawi AR, Al-Badri SAF, Al-Darraji AF, Al-Saeed RM, Al-Hadad SA, and Lovvorn Iii HN
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Apoptosis Regulatory Proteins, Child, Preschool, DNA Topoisomerases, Type II genetics, Female, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Immunohistochemistry, Infant, Insulin-Like Growth Factor II genetics, Iraq, Kidney Neoplasms pathology, Male, Multiplex Polymerase Chain Reaction, Mutation, N-Myc Proto-Oncogene Protein genetics, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neural Cell Adhesion Molecules metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Poly-ADP-Ribose Binding Proteins genetics, Receptors, Retinoic Acid genetics, Sequence Analysis, DNA methods, Trans-Activators, Transcription Factors genetics, Transcription Factors metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Proteins genetics, WT1 Proteins genetics, WT1 Proteins metabolism, Wilms Tumor pathology, beta Catenin genetics, beta Catenin metabolism, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Wilms Tumor genetics, Wilms Tumor metabolism
- Abstract
Background: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. To guide and streamline therapy in the war-torn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population., Methods: Next-generation sequencing of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled., Results: Mutations were detected in previously described WT "hot spots" (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range 6-78 months)., Conclusions: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.
- Published
- 2018
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