Cancer Health Center

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Wilms tumor gene on the X chromosome (WTX)

A third gene, WTX, has been identified on the X chromosome and plays a role in normal kidney development. WTX mutations were identified in 17% of Wilms tumors, equally distributed between males and females.[45] This gene is inactivated in approximately one-third of Wilms tumors but germline mutations have not been observed in patients with Wilms tumor.[46]

Other genes

Additional genes have been implicated in the pathogenesis and biology of Wilms tumor:

• 16q and 1p: Additional tumor-suppressor or tumor-progressive genes may lie on chromosomes 16q and 1p as evidenced by LOH for these regions in 17% and 11% of Wilms tumors, respectively. Patients classified by tumor-specific loss of these loci had significantly worse relapse-free and overall survival rates. Combined loss of 1p and 16q are used to select favorable-histology Wilms tumor patients for more aggressive therapy in the current Children's Oncology Group study.[47]
• CACNA1E: Overexpression and amplification of the gene CACNA1E located at 1q25.3, which encodes the ion-conducting alpha-1 subunit of R-type voltage-dependent calcium channels, may be associated with relapse in favorable-histology Wilms tumor.[48]
• 7p21: A consensus region of LOH has been identified within 7p21 containing ten known genes, including two candidate suppressor genes (Mesenchyme homeobox 2 [MEOX2] and Sclerostin domain containing 1 [SOSTDC1]).[49]
• SKCG-1: Genomic loss of a growth regulatory gene, SKCG-1, located at 11q23.2, was found in 38% of examined sporadic Wilms tumors and particularly the highly proliferative Wilms tumors. Additional studies of si-RNA silencing of the SKCG-1 gene in human embryonic kidney epithelial cells resulted in a 40% increase in cell growth, which suggests that this gene may be involved in loss of growth regulation and Wilms tumorigenesis.[50]
• p53 tumor suppressor gene: A small subset of anaplastic Wilms tumors show mutations in the p53 tumor suppressor gene. Although it is unlikely that it plays a major role in Wilms tumorigenesis, it may be useful as an unfavorable prognostic marker.[51,52]
• FBXW7: FBXW7, a ubiquitin ligase component, has been identified as a novel Wilms tumor gene. Mutations of this gene have been associated with epithelial-type tumor histology.[53]
• MYCN: Genomic gain or amplification of MYCN is relatively common in Wilms tumors and associated with diffuse anaplastic histology.[53]

Genetics of Familial Wilms Tumor

Despite the number of genes that appear to be involved in the development of Wilms tumor, hereditary Wilms tumor is uncommon, with approximately 2% of patients having a positive family history for Wilms tumor. Siblings of children with Wilms tumor have a low likelihood of developing Wilms tumor.[54] The risk of Wilms tumor among offspring of persons who have had unilateral (sporadic) tumors is less than 2%.[55] Two familial Wilms tumor genes have been localized to FWT1 (17q12-q21) and FWT2 (19q13.4).[56,57,58]