Localization
kidney (renal Wilms tumor)
extrarenal Wilms tumor
Macroscopical variants
solid Wilms tumor
cystic Wilms tumor
botryoid Wilms tumor
post-chemotherapy Wilms tumor
Microscopical variants
anaplastic Wilms tumor (anaplasia in Wilms tumor)
Wilms tumor with teratomatous cysts
Epidemiological variants
Wilms tumor arising in a germ cell tumor (15105660)
bilateral Wilms tumor (multiple Wilms tumor)
adult Wilms tumor
Associations
juxtaposed cystic nephroma and Wilms tumor (10594137)
Predisposition syndrome
aniridia, WAGR syndrome (WT1 locus at 11p13)
Drash syndrome (WT1 locus at 11p13)
Beckwith-Wiedemann syndrome (BWS) (11p15.5)
trisomy 18 (7700182, 12900902)
monosomy X (Turner syndrome) (7700182)
constitutional translocation t(1;7)(q42;p15)
constitutional translocation t(7;19)(q11.2;q13.3)
- with thick corpus callosum, enlarged cisterna magna, normal vermis, thick corpus callosum, micrognathia, small and low-set ears (16193462)
Fanconi syndrome +/- BRCA2 biallelic mutations (14670928)
Cytogenetics
- target regions: 1q21, 1q42, 2p25, 5q21, 6q21, 7p13, 7p15, 7q11, 7q36, 11p11, 11p13, 11p15, 12q13, 13q13, 15q21, 16q13, 19q13, Chr.X, Chr.20, 22q12
constitutional 6q21 rearrangements
constitutional t(7;19)(q11;q13) (16193462)
constitutional t(7;13)(q36;q13) (6321191)
- facial dysmorphism with hydrocephaly and mental retardation (6321191)
7p15 rearrangements (PTHB locus)
11p13 rearrangements (WAGR)
- constitutional t(2;11)(p25;p13) (12845852)
- constitutional t(5;11)(q11;p13) (2838157)
- constitutional t(11;22)(p13;q12) (3754537)
- del(11)(p11p13) (2550862)
- aniridia and genitourinary abnormalities
miscellaneous tumoral translocations
- target regions: 1q21, 7p13, 11p11, 11p15, 12q13, 16q13, Chr.X, Chr.20
- tumoral t(1;16)(q21;q13) (8614388)
- tumoral t(7;7)(p13;q21) (8397065)
- tumoral t(11;12)(p11;q13) (2550862)
- tumoral t(X;20) (2154323)
- tumoral t(11;11)(p13;p15) (2838157)
CGH
| Gains | +1q | +6 | +7q | +8 | +12 | +13 |
| Losses | -11 | -16 |
Gain of 1q is associated with adverse outcome in favorable histology Wilms’ tumors (11159177)
Allelotyping (LOH)
| LOH | % | Target genes | References | ||
| 1p LOH | 9.5% | unknown | 9669666, 17243164 | ||
| 4q LOH | 5% | unknown | 9669666 | ||
| 6p LOH | 6% | unknown | 9669666 | ||
| 7p31-p14 LOH | 3-25 | POU6F2 | 9690521 | 10646884 | 15459955 |
| 9q22.2-q31.1 LOH | - | - | 15761866 | ||
| 11p13 LOH | 17-25% | WT1 | 9669666 | ||
| 11p15.5 LOH | 28% | H19, P57KIP2 | 9669666 | ||
| 11q LOH | 10% | unknown | 9669666 | ||
| 16q22 LOH | 4%-13% | unknown | 9669666 | 12620908 | |
| 18p LOH | 9% | unknown | 9669666 | ||
| 22q LOH | 14% | unknown | 9669666 |
Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology wilms tumor (16129848) Genic mutations
germline and somatic mutations of WT1 at 11p13 (mutational inactivation) (10-20% of sporadic tumors)
somatic mutations of CTNNB1 coding for beta-catenin at 3p22-21 (mutational activation) (14% of sporadic tumors) (10463574, 11103785)
WNT/beta-catenin pathway deregulation (17691963)
Beta-catenin gain-of-function mutations are strongly linked to WT1 loss-of-function mutations in syndromic Wilms tumors, and Wnt/beta-catenin signaling increases androgen receptor mRNA expression and blocks apoptosis in prostate cancers.
Novel downstream target genes activated by Wnt/beta-catenin signaling are emerging from expression profiling in genetically defined classes of Wilms tumors
The WNT/beta-catenin pathway is involved in numerous human cancers. Somatic mutations of the CTNNB1 (beta-catenin) gene have also been detected in a subset of pediatric Wilms tumor.
CTNNB1 somatic mutations
PITX2, APCDD1, and two members of the endothelin axis (EDN3 and EDNRA) are directly activated downstream targets of the WNT/beta-catenin pathway that may enhance proliferation of these tumor cells. (16575872)
Several upstream inhibitors of WNT/beta-catenin signaling like WIF1 and PRDC were also strongly up-regulated in the CTNNB1-mutated Wilms tumors. (16575872)
Deregulated genes have been detected in both the retinoic acid and the RAS pathways, such as ATX/ENPP2 and RIS1, suggesting an association between these two pathways with that of WNT. (16575872)
The strong representation of muscle-related genes in the expression profile of CTNNB1-mutated Wilms tumors corresponded to histologically detectable areas of myomatous cells in these tumors that displayed intense and preferential nuclear beta-catenin antibody staining. (16575872)
References
Tamimi Y, Ziebart K, Desaulniers N, Dietrich K, Grundy P. Identification of a minimal region of loss on the short arm of chromosome 1 in Wilms tumor. Genes Chromosomes Cancer. 2007 Jan 22;46(4):327-335. PMID: 17243164
Wittmann S, Zirn B, Alkassar M, Ambros P, Graf N, Gessler M. Loss of 11q and 16q in Wilms tumors is associated with anaplasia, tumor recurrence, and poor prognosis. Genes Chromosomes Cancer. 2007 Feb;46(2):163-70. PMID: 17099873
Zirn B, Samans B, Wittmann S, Pietsch T, Leuschner I, Graf N, Gessler M. Target genes of the WNT/beta-catenin pathway in Wilms tumors. Genes Chromosomes Cancer. 2006 Jun;45(6):565-74. PMID: 16575872
Watanabe N, Nakadate H, Haruta M, Sugawara W, Sasaki F, Tsunematsu Y, Kikuta A, Fukuzawa M, Okita H, Hata J, Soejima H, Kaneko Y. Association of 11q loss, trisomy 12, and possible 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor. Genes Chromosomes Cancer. 2006 Jun;45(6):592-601. PMID: 16518847
Reviews
Tycko B, Li CM, Buttyan R. The Wnt/beta-catenin pathway in Wilms tumors and prostate cancers. Curr Mol Med. 2007 Aug;7(5):479-89. Review. PMID: 17691963
Rivera MN, Haber DA. Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer. 2005 Sep;5(9):699-712. PMID: 16110318
Dome JS, Coppes MJ. Recent advances in Wilms tumor genetics. Curr Opin Pediatr. 2002 Feb;14(1):5-11. PMID: 11880727
