Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq.

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, Lovvorn Iii HN
World J Pediatr. 2018 14 (6): 585-593

PMID: 30155617 · PMCID: PMC6236303 · DOI:10.1007/s12519-018-0181-3

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.

MeSH Terms (27)

Adaptor Proteins, Signal Transducing beta Catenin Child, Preschool DNA Topoisomerases, Type II Female Homeodomain Proteins Humans Immunohistochemistry Infant Insulin-Like Growth Factor II Iraq Kidney Neoplasms Male Multiplex Polymerase Chain Reaction Mutation N-Myc Proto-Oncogene Protein Nerve Tissue Proteins Neural Cell Adhesion Molecules Nuclear Proteins Poly-ADP-Ribose Binding Proteins Receptors, Retinoic Acid Sequence Analysis, DNA Transcription Factors Tumor Suppressor Protein p53 Tumor Suppressor Proteins Wilms Tumor WT1 Proteins

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