Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq

• Published in: World journal of pediatrics : WJP Vol. 14; no. 6; pp. 585 - 593
• Main Authors: Phelps, Hannah M., Al-Jadiry, Mazin F., Corbitt, Natasha M., Pierce, Janene M., Li, Bingshan, Wei, Qiang, Flores, Raina R., Correa, Hernan, Uccini, Stefania, Frangoul, Haydar, Alsaadawi, Adel R., Al-Badri, Safaa A. F., Al-Darraji, Amir F., Al-Saeed, Raghad M., Al-Hadad, Salma A., Lovvorn III, Harold N.
• Format: Journal Article
• Language: English
• Published: Hangzhou Childrens Hospital, Zhejiang University School of Medicine 01-12-2018; Vanderbilt University School of Medicine,2215 Garland Avenue,Nashville,TN 37232-9780,USA%Oncology Unit,Children's Welfare Teaching Hospital,Baghdad University Medical City,Baghdad,Iraq%Department of Pediatric Surgery,Vanderbilt University Medical Center,Nashville,USA%Department of Molecular Physiology and Biophysics,Vanderbilt University School of Medicine,Nashville,USA%Division of P ediatric Pathology,Vanderbilt UniversityMedical Center,Nashville,USA%Department of Clinical and Molecular Medicine,SapienzaUniversity,Rome,Italy%Division of P ediatric Hematology and Oncology,VanderbiltUniversity Medical Center,Nashville,USA%Department of P athology,Baghdad University Medical City,Baghdad,Iraq%Oncology Unit,Children's Welfare Teaching Hospital,WasitUniversity College of Medicine,Wasit,Iraq
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Apoptosis Regulatory Proteins; beta Catenin - genetics; beta Catenin - metabolism; Child, Preschool; Critical Care Medicine; DNA Topoisomerases, Type II - genetics; Female; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Imaging; Immunohistochemistry; Infant; Insulin-Like Growth Factor II - genetics; Intensive; Iraq; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Male; Maternal and Child Health; Medicine; Medicine & Public Health; 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; Original Article; Pediatric Surgery; Pediatrics; Poly-ADP-Ribose Binding Proteins - genetics; Radiology; Receptors, Retinoic Acid - genetics; Sequence Analysis, DNA - methods; Surgery; Trans-Activators; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - genetics; Wilms Tumor - genetics; Wilms Tumor - metabolism; Wilms Tumor - pathology; WT1 Proteins - genetics; WT1 Proteins - metabolism; Iraq; Pediatric cancer; Next-generation sequencing; Iraq; Low- and middle-income countries; Wilms tumor
• ISSN: 1708-8569; 1867-0687
• 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.