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

Autor: Phelps HM; Vanderbilt University School of Medicine, 2215 Garland Avenue, Nashville, TN, 37232-9780, USA. hannah.m.phelps@vanderbilt.edu., Al-Jadiry MF; Oncology Unit, Children's Welfare Teaching Hospital, Baghdad University Medical City, Baghdad, Iraq., Corbitt NM; Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, USA., Pierce JM; Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, USA., Li B; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, USA., Wei Q; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, USA., Flores RR; Division of Pediatric Pathology, Vanderbilt University Medical Center, Nashville, USA., Correa H; Division of Pediatric Pathology, Vanderbilt University Medical Center, Nashville, USA., Uccini S; Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy., Frangoul H; Division of Pediatric Hematology and Oncology, Vanderbilt University Medical Center, Nashville, USA., Alsaadawi AR; Department of Pathology, Baghdad University Medical City, Baghdad, Iraq., Al-Badri SAF; Oncology Unit, Children's Welfare Teaching Hospital, Wasit University College of Medicine, Wasit, Iraq., Al-Darraji AF; Oncology Unit, Children's Welfare Teaching Hospital, Baghdad University Medical City, Baghdad, Iraq., Al-Saeed RM; Oncology Unit, Children's Welfare Teaching Hospital, Baghdad University Medical City, Baghdad, Iraq., Al-Hadad SA; Oncology Unit, Children's Welfare Teaching Hospital, Baghdad University Medical City, Baghdad, Iraq., Lovvorn Iii HN; Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, USA.
Jazyk: angličtina
Zdroj: World journal of pediatrics : WJP [World J Pediatr] 2018 Dec; Vol. 14 (6), pp. 585-593. Date of Electronic Publication: 2018 Aug 28.
DOI: 10.1007/s12519-018-0181-3
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: