Wilms Tumor


Wilms tumor, otherwise known as nephroblastoma, is a childhood embryonal kidney cancer. This potentially heritable tumor involves several different genes, many of which illustrate the close relationship between cancer and maldevelopment. The majority of children are cured of their cancer but new molecular markers to predict tumor recurrence risk are needed to allow better stratification of treatment intensity.

Keywords: embryonal cancer; WT1 gene; nephrogenesis (or kidney development); imprinting; nephrotic syndrome; familial cancer; childhood cancer

Figure 1.

Wilms tumor shows remarkable mimicry of the nephrogenic process. The left panel shows the nephrogenic zone of an 18‐week gestation human fetal kidney. There is orderly differentiation of the primitive blastema into tubular (epithelial) components in response to reciprocal inductive signals from the branching ureteric bud. The right panel shows a classic triphasic Wilms tumor in which all three cell types (primitive blastema, epithelia and stroma) are seen. In this particular tumor, epithelial differentiation is proceeding as far as an attempt to make pseudoglomeruli.

Figure 2.

Intralobar nephrogenic rest (ILNR). ILNRs are regions of residual primitive nephrogenic tissue thought to arise at an early stage of nephrogenesis. As in this case (white arrow), they usually lie immediately adjacent to the associated Wilms tumor (black arrow), the latter often showing prominent stromal differentiation. ILNRs usually mimic the entire spectrum of renal histogenesis, are usually single and are thought to have a high tumorigenic potential. (Photograph courtesy of Dr Gordan Vujanic, University Hospital of Wales, Cardiff.)

Figure 3.

Perilobar nephrogenic rest (PLNR). A PLNR (white arrow) is a well‐circumscribed area of incompletely differentiated fetal renal tissue. These are usually found at the periphery of the renal lobule, are often multiple and show restricted differentiation potential, mimicking late stages of nephrogenesis with mainly tubular differentiation. The associated Wilms tumors (black arrow) usually have restricted, mainly epithelial differentiation. (Photograph courtesy of Dr Gordan Vujanic, University Hospital of Wales, Cardiff.)

Figure 4.

Age distribution of Wilms tumor in relation to bilaterality and type of associated nephrogenic rest (a) unilateral unicentric tumors; (b) bilateral tumors; (c) unilateral, multicentric tumors. (Data courtesy of Professor Norman Breslow and the National Wilms Tumor Study Group, North America.)

Figure 5.

Structure of the WT1 gene, showing the position of the two alternative splice sites, comprising the whole of exon 5 and the additional amino acids, KTS, in the linker between the third and fourth zinc‐fingers. The position of two commonly mutated arginine residues in Denys–Drash syndrome is indicated (R366 and R394) – these residues are critical for DNA binding by these zinc‐fingers. The N‐terminal transcriptional regulatory domains defined by in vitro studies are indicated, the dotted line indicates the possible usage of an alternative initiation codon.



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Breslow N, Olshan A, Beckwith JB and Green DM (1993) Epidemiology of Wilms tumor. Medical and Pediatric Oncology 21: 172–181.

Charles AK, Brown KW and Berry PJ (1998) Microdissecting the genetic events in nephrogenic rests and Wilms' tumor development. American Journal of Pathology. 153: 991–1000.

DeBaun MR, Niemitz EL, McNeil DE, et al. (2002) Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith–Wiedemann syndrome with cancer and birth defects. American Journal of Human Genetics 70: 604–611.

DeBaun MR, Siegel MJ, Choyke PL, et al. (1998) Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith–Wiedmann syndrome. Journal of Pediatrics 132: 401–404.

Green DM, Breslow NE, Beckwith JB, et al. (1998) Effect of duration of treatment on treatment outcome and cost of treatment for Wilms tumour: a report from the National Wilms Tumour Study Group. Journal of Clinical Oncology 16: 3744–3751.

Grundy P, Telzerow P, Moksness J and Breslow NE (1996) Clinicopathologic correlates of loss of heterozygosity in Wilms tumor: a preliminary analysis. Medical and Pediatric Oncology. 27: 429–433.

Hastie ND (1994) The genetics of Wilms' tumor: a case of disrupted development. Annual Review of Genetics 28: 523–558.

Hawkins MM, Winter DL, Burton HS, et al. (1995) Heritability of Wilms' tumour. Journal of the National Cancer Institute 87: 1323–1324.

Pelletier J, Bruening W, Kashtac CE, et al. (1991) Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogential development in Denys–Drash syndrome. Cell 67: 437–447.

Rahman N, Arbour L, Tonin P, et al. (1996) Evidence for a familial Wilms' tumour gene (FWT1) on chromosome 17q12–q211. Nature Genetics 13: 461–463.

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Tournade MF, Com‐Nougue C, Voute PA, et al. (1993) Results of the sixth International Society of Paediatric Oncology Wilms Tumour Trial and Study: a risk‐adapted therapeutic approach in Wilms tumour. Journal of Clinical Oncology 11: 1014–1023.

Further Reading

Choyke PL, Siegel MJ, Craft AW, et al. (1999) Screening for Wilms tumor in children with Beckwith–Wiedemann syndrome or idiopathic hemihypertrophy. Medical and Pediatric Oncology 32: 196–200.

Hammes A, Guo JK, Lutsch G, et al. (2001) Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell 106: 319–329.

Koziell A, Charmandari E, Hindmarsh PC, et al. (2000) Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy? Clinical Endocrinology 52: 519–524.

Kreidberg JA, Sariola H, Loring JM, et al. (1993) WT‐1 is required for early kidney development. Cell 74: 679–691.

Little M, Holmes G and Walsh P (1999). WT1: what has the last decade told us? BioEssays 21: 191–202.

Pritchard‐Jones K (1997) Molecular genetic pathways to Wilms tumour. Critical Reviews in Oncogenesis 8: 1–27.

Schumacher V, Schneider S, Figge A, et al. (1997) Correlation of germ‐line mutations and two‐hit inactivation WT1 gene with Wilms tumors of stromal‐predominant histology. Proceedings of the National Academy of Sciences of the United States of America 94: 3972–3977.

Veugelers M, De Cat B, Muyldermans SY, et al. (2000) Mutational analysis of the GPC3/GPC4 glypican gene cluster on Xq26 in patients with Simpson–Golabi–Behmel syndrome: identification of loss‐of‐function mutations in the GPC3 gene. Human Molecular Genetics 9: 1321–1328.

Web Links

Database of WT1 mutations. http://archive.uwcm.ac.uk/uwcm/mg/hgmd0.html

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Pritchard‐Jones, Kathy(Jan 2006) Wilms Tumor. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006052]