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Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq

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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.

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Acknowledgements

The authors would like to thank Travis Clark and Holli Dicks for their technical assistance to conduct the next-generation sequencing analysis of these specimens.

Funding

This work was supported in part by the Carolyn Perot Rathjen Chair in Pediatrics at Vanderbilt (HF), the NIH/NCRR (Grant number G20 RR030956—VANTAGE Shared Resource at Vanderbilt), the NIH/NCI (Grant number 5R21CA155946-02), and the Vanderbilt Ingram Cancer Center Support Grant number 5P30 CA068485 (Translational Pathology Shared Resource).

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Authors and Affiliations

  1. Vanderbilt University School of Medicine, 2215 Garland Avenue, Nashville, TN, 37232-9780, USA

    Hannah M. Phelps

  2. Oncology Unit, Children’s Welfare Teaching Hospital, Baghdad University Medical City, Baghdad, Iraq

    Mazin F. Al-Jadiry, Amir F. Al-Darraji, Raghad M. Al-Saeed & Salma A. Al-Hadad

  3. Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, USA

    Natasha M. Corbitt, Janene M. Pierce & Harold N. Lovvorn III

  4. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, USA

    Bingshan Li & Qiang Wei

  5. Division of Pediatric Pathology, Vanderbilt University Medical Center, Nashville, USA

    Raina R. Flores & Hernan Correa

  6. Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy

    Stefania Uccini

  7. Division of Pediatric Hematology and Oncology, Vanderbilt University Medical Center, Nashville, USA

    Haydar Frangoul

  8. Department of Pathology, Baghdad University Medical City, Baghdad, Iraq

    Adel R. Alsaadawi

  9. Oncology Unit, Children’s Welfare Teaching Hospital, Wasit University College of Medicine, Wasit, Iraq

    Safaa A. F. Al-Badri

Authors
  1. Hannah M. Phelps
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  2. Mazin F. Al-Jadiry
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  3. Natasha M. Corbitt
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  4. Janene M. Pierce
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  5. Bingshan Li
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  11. Adel R. Alsaadawi
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  14. Raghad M. Al-Saeed
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  15. Salma A. Al-Hadad
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  16. Harold N. Lovvorn III
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Contributions

HMP wrote the manuscript, interpreted the data, and provided administrative and technical support. MFA designed the study, acquired data, provided administrative and technical support, and supervised the study. NMC wrote the manuscript, interpreted the data, and provided administrative and technical support. JMP developed the study methodology, acquired data, analyzed and interpreted the data, and provided administrative and technical support. BL analyzed and interpreted the data. QW analyzed and interpreted the data. RRF acquired data. HC acquired data. SU acquired data and provided administrative and technical support. HF designed the study. ARA acquired data and provided administrative and technical support. SAFA acquired data and provided administrative and technical support. AFA acquired data and provided administrative and technical support. RMA acquired data and provided administrative and technical support. SAA acquired data and provided administrative and technical support. HNL designed the study, developed the methodology, analyzed and interpreted the data, wrote the manuscript, and supervised the study. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Hannah M. Phelps.

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Ethical approval

Approval to conduct these studies was provided through the Vanderbilt Institutional Review Board (#100734 and #020888).

Conflict of interest

The authors have no conflict of interests to disclose. No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

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Phelps, H.M., Al-Jadiry, M.F., Corbitt, N.M. et al. Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq. World J Pediatr 14, 585–593 (2018). https://doi.org/10.1007/s12519-018-0181-3

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  • DOI: https://doi.org/10.1007/s12519-018-0181-3

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