What causes Wilms' tumor?
Last reviewed: 20.11.2021
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Wilms tumor (nephroblastoma) is a malignant embryonic neoplasm of the kidney. On nefroblastomu about 6% of all malignant neoplasms in children, this is the most frequent kidney tumor, the second most frequently extracranial solid tumor of childhood and the second most frequent malignant tumor of the retroperitoneal space. Bilateral involvement is observed in 5-6% of cases. The incidence of nephroblastoma is 9 cases per 1,000,000 children. Girls and boys get sick with the same frequency. The peak incidence falls on the age of 3-4 years. In 70% of cases, Wilms' tumor occurs in children aged 1-6 years, in 2% - in newborns (usually in a benign variant). Sporadic cases of nephroblastoma are usually observed, but 1% of patients reveal a family predisposition.
Causes and pathogenesis of Wilms tumor
The link with developmental malformations has become the key to discovering the genetic nature of Wilms' tumor. An important role in the pathogenesis of nephroblastoma is played by recessive tumor genes (suppressor genes). Cytogenetic studies and methods of molecular analysis have made it possible to determine polymorphism, homozygosity or heterozygosity of genes. The loss of heterozygosity leads to the activation of the tumor suppressor gene and triggers the development of a malignant process.
In the cells of Wilms tumor, a deletion in the short arm of the chromosome 11 (11p13) was identified. The W1 gene of the Wilms tumor encodes a transcription factor that determines the normal development of renal tissue and gonads. A pathological linear mutation involving the MP gene was identified in patients with WAGR syndrome and Denis-Drash syndrome, as well as in patients with bilateral nephroblastoma. A specific mutation of the WTI gene is found in 10% of patients with a sporadic Wilms tumor.
The second gene of the Wilms tumor (WT2) is located at the locus 11p15.5, this gene causes loss of specific heterozygosity by the cells, which leads to a tumor progression. The same chromosomal abnormality is determined in patients with Bekuit-Wiedemann syndrome and hemyhypertrophy. The gene WT2 is inherited by the female line, it is formed due to genomic imprinting.
In 20% of patients with Wilms' tumor, the allelic loss of the long arm of the 16th chromosome is revealed. Assume the existence of a family nephroblastoma gene, but localization has not yet been established.