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Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq

World Journal of Pediatrics 2018年第6期14卷 585-593页

作者： Hannah M.Phelps Mazin F.Al-Jadiry Natasha M.Corbitt Janene M.Pierce Bingshan Li Qiang Wei Raina R.Flores Hernan Correa Stefania Uccini Haydar Frangoul Adel R.Alsaadawi Safaa A.F.Al-Badri Amir F.Al-Darraji Raghad M.Al-Saeed Salma A.Al-Hadad Harold N.LovvornⅢ Vanderbilt University School of Medicine 2215 Garland AvenueNashvilleTN 37232-9780USA Oncology Unit Children’s Welfare Teaching HospitalBaghdad University Medical CityBaghdadIraq Department of P ediatric Surgery Vanderbilt University Medical CenterNashvilleUSA Department of Molecular Physiology and Bioph ysics Vanderbilt University School of MedicineNashvilleUSA Division of P ediatric Pathology Vanderbilt University Medical CenterNashvilleUSA Department of Clinical and Molecular Medicine Sapienza UniversityRomeItaly Division of P ediatric Hematology and Oncology Vanderbilt University Medical CenterNashvilleUSA Department of P athology Baghdad University Medical CityBaghdadIraq Oncology Unit Children’s Welfare Teaching HospitalWasit University College of MedicineWasitIraq

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.

关键词： Iraq low- and middle-income countries Next-generation sequencing Pediatric cancer Wilms tumor

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