Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq

被引:6
作者
Phelps, Hannah M. [1 ]
Al-Jadiry, Mazin F. [2 ]
Corbitt, Natasha M. [3 ]
Pierce, Janene M. [3 ]
Li, Bingshan [4 ]
Wei, Qiang [4 ]
Flores, Raina R. [5 ]
Correa, Hernan [5 ]
Uccini, Stefania [6 ]
Frangoul, Haydar [7 ]
Alsaadawi, Adel R. [8 ]
Al-Badri, Safaa A. F. [9 ]
Al-Darraji, Amir F. [2 ]
Al-Saeed, Raghad M. [2 ]
Al-Hadad, Salma A. [2 ]
Lovvorn, Harold N., III [3 ]
机构
[1] Vanderbilt Univ, Sch Med, 2215 Garland Ave, Nashville, TN 37232 USA
[2] Baghdad Univ Med City, Childrens Welf Teaching Hosp, Oncol Unit, Baghdad, Iraq
[3] Vanderbilt Univ, Med Ctr, Dept Pediat Surg, Nashville, TN USA
[4] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Div Pediat Pathol, Nashville, TN USA
[6] Sapienza Univ, Dept Clin & Mol Med, Rome, Italy
[7] Vanderbilt Univ, Med Ctr, Div Pediat Hematol & Oncol, Nashville, TN USA
[8] Baghdad Univ Med City, Dept Pathol, Baghdad, Iraq
[9] Wasit Univ, Childrens Welf Teaching Hosp, Oncol Unit, Coll Med, Wasit, Iraq
关键词
Iraq; Low- and middle-income countries; Next-generation sequencing; Pediatric cancer; Wilms tumor; MUTATIONS; EXPRESSION; CITED1; P53; PROGNOSIS; ONCOGENE; CATENIN; CANCER; GENES; SIX2;
D O I
10.1007/s12519-018-0181-3
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
BackgroundWilms 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.MethodsNext-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.ResultsMutations 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 40.5months (range 6-78months).ConclusionsThese 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.
引用
收藏
页码:585 / 593
页数:9
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