Wilms Tumor Panel

Wilms tumor is the most common pediatric kidney cancer. It affects nearly 1 in 10,000 children (Mahamdallie et al. 2019. PubMed ID: 30885698). Clinical features of an affected individual can include an abdominal mass, pain, fever, anemia, hematuria and hypertension. Most individuals present with unilateral kidney tumors. Approximately 5-10% of individuals present with bilateral or multifocal tumors of the kidneys. Wilms tumor usually presents before the age of 5, but it has also been initially observed in older individuals. Although patients may present with isolated Wilms tumor, individuals may present with additional clinical features such as those affected with WAGR syndrome (Wilms tumor, aniridia, genital anomalies, range of developmental delays), Denys-Drash syndrome, Frasier syndrome, and Wilms tumor with genitourinary anomalies without renal failure (Dome et al. 1993. PubMed ID: 20301471). Other disorders that have an increased risk of Wilms tumor include Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome, Perlman syndrome, and Li-Fraumeni syndrome (Mahamdallie et al. 2019. PubMed ID: 30885698). Identification of a germline predisposition to Wilms tumor is important for treatment (e.g. surgery, chemotherapy, radiation) and screening (e.g. imaging studies) (Dome et al. 1993. PubMed ID: 20301471).

Wilms tumor generally occurs sporadically, but approximately 2% of individuals have a family member with the tumor, suggesting a hereditary cause of disease (Scott et al. 2006. PubMed ID: 16690728). For cases that are thought to be due to an underlying genetic cause, testing for pathogenic variants in just the WT1 gene is often performed. However, recent literature suggests that pathogenic variants in a number of genes, including FBXW7, KDM3B, NYNRIN, TRIM28 and others significantly increase an individual’s risk for developing Wilms tumor (Mahamdallie et al. 2019. PubMed ID: 30885698). Most of these pathogenic variants are inherited in an autosomal dominant manner, but there are several autosomal recessive and X-linked disorders that increase the risk of developing Wilms tumor.

Many of these genes in the panel are tumor suppressors, and others are involved in nucleic acid metabolism, chromosome organization, and chromatin or histone modification (Mahamdallie et al. 2019. PubMed ID: 30885698).

See individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.

Most Wilms tumors are sporadic; however, testing for germline pathogenic variants in this panel is thought to account for 10-20% of Wilms tumor cases (Md Zin et al. 2011. PubMed ID: 21516053; Mahamdallie et al. 2019. PubMed ID: 30885698). Most individuals with Denys-Drash syndrome have a germline WT1 missense pathogenic variant in exon 8 or 9 (Martínez et al. 2010. PubMed ID: 20687507). Frasier syndrome is caused by pathogenic variants in the WT1 intron 9 donor splice site (Barbaux et al. 1997. PubMed ID: 9398852). Large deletions are found in WAGR syndrome and infrequently in isolated Wilms tumor (Schumacher et al. 1997. PubMed ID: 9108089).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.1% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).