Genetic and chromosomal alterations in Kenyan Wilms Tumor

Area of Science:

• Pediatric Oncology
• Genomics
• Cancer Health Disparities

Background:

• Wilms tumor (WT) is the most common childhood kidney cancer globally.
• WT survival exceeds 90% in developed nations but is significantly lower in sub-Saharan Africa, particularly Kenya (36% at 2 years).
• Existing barriers to care are compounded by a hypothesized aggressive WT biology in Kenyan patients.

Purpose of the Study:

• To investigate the genomic characteristics of Kenyan Wilms tumor (KWT) to understand its aggressive and treatment-resistant biology.
• To identify specific genetic mutations and copy number variations associated with poor outcomes in KWT.

Main Methods:

• Next-generation sequencing of 10 WT-associated genes in 44 KWT specimens.
• Whole-genome copy number variation analysis.
• Evaluation of mutations including TP53, CTNNB1, MYCN, AMER1, WT1, TOP2A, and IGF2, and copy number alterations such as 1q gain and 11q LOH.

Main Results:

• TP53 mutations were found in 25% of KWT, CTNNB1 in 23%, and MYCN in 18%.
• Loss of heterozygosity (LOH) at 17p (covering TP53) was detected in 18% of samples.
• Copy number gain at 1q, a known poor prognostic indicator, was present in 32% of KWT, with 89% of these children deceased. LOH at 11q was also observed in 32% of KWT, with 80% mortality.

Conclusions:

• Kenyan Wilms tumor exhibits a uniquely aggressive genomic profile, characterized by frequent TP53 mutations and a high prevalence of poor prognostic markers like 1q gain.
• These biological factors likely contribute significantly to the poor survival rates observed in Kenyan children with WT.
• Further research into targeted therapies addressing these specific genomic alterations is warranted to improve outcomes for pediatric cancer patients in Kenya.