Molecular-Genetic Profile of Nephroblastoma in Children in Uzbekistan: Clinical-Morphological Correlations and the Prognostic Significance of K-RAS Mutations.
Keywords:
Nephroblastoma, Wilms Tumor, K-Ras, Children, Organ Invasion, Metastasis, Relapse, Uzbekistan..Abstract
Relevance. Nephroblastoma remains one of the leading malignant tumors of childhood. In a subset of patients, despite standard SIOP/COG protocols, early relapses and metastases occur, which are associated with unfavorable molecular profiles, including activation of the RAS/MAPK cascade and K-RAS mutations. Data on the pediatric population of Uzbekistan have previously been unavailable.
Objective of the study. To assess the frequency of K-ras gene mutations in children with nephroblastoma in Uzbekistan and to determine their association with tumor stage, organ invasion, metastasis, and treatment characteristics
Materials and methods. A retrospective analysis was conducted on 230 patients under 15 years of age with histologically confirmed nephroblastoma who were treated at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology and its branches. Clinical and morphological parameters, Enneking stage, surgical volume, therapy regimens, recurrences, and regional and distant metastases were evaluated. K-ras mutations (codons 12 and 13) were identified using Sanger sequencing and/or NGS. Statistical analysis included χ² testing, with p < 0.05 considered significant.
Results. K-ras mutations were detected in 23 (10.0%) of the 230 patients. Their frequency increased with age and tumor stage, reaching 76.5% in stage IV. Mutations were significantly more common in cases of relapse (33.3% vs. 2.3%), in the presence of regional (15.7% vs. 6.6%) and distant metastases (36.4% vs. 3.8%), as well as in patients who received only chemotherapy and palliative interventions.
Conclusion. K-ras mutation is a rare but highly informative marker of aggressive nephroblastoma, associated with advanced stages, organ invasion, relapse, and metastasis. Incorporating K-ras analysis into the risk stratification system for children with nephroblastoma in Uzbekistan may improve individualized treatment and the accuracy of prognostic assessment.
