Recent advances in Wilms' tumor predisposition.

Area of Science:

• Pediatric Oncology
• Cancer Genetics
• Genomics

Background:

• Wilms tumor (WT) is the most frequent pediatric kidney cancer, with germline predisposition identified in up to 15% of cases.
• Known genetic factors include WT1 gene alterations and 11p15 locus epigenetic changes, alongside broader cancer predispositions like Li-Fraumeni and Bloom syndrome.

Purpose of the Study:

• To review current evidence on germline genetic factors contributing to Wilms tumor predisposition.
• To highlight the roles of WT1, the 11p15 locus, and newly identified genes (CTR9, REST, TRIM28) in WT development.
• To emphasize the clinical importance of genetic diagnosis for surveillance and treatment optimization in WT families.

Main Methods:

• Review of recent germline genomic investigations, including sequencing of rare familial cases and large WT cohorts.
• Analysis of evidence implicating specific genes and genetic loci in Wilms tumor predisposition.
• Discussion of clinical features, inheritance patterns, and tumorigenesis mechanisms.

Main Results:

• Germline alterations in WT1 and epigenetic changes at 11p15 are established WT risk factors.
• Emerging evidence implicates CTR9, REST, and TRIM28 as additional Wilms tumor predisposition genes.
• Despite advances, a significant proportion of familial Wilms tumor cases remain genetically unexplained.

Conclusions:

• Genetic predisposition plays a crucial role in a subset of Wilms tumor cases.
• Continued research is essential to fully map the genetic landscape of WT.
• Genetic diagnosis is critical for implementing surveillance protocols, enabling early tumor detection and less intensive treatment strategies, ultimately improving patient outcomes.