Monday 18 June 2007
WTX (or FAM123B) is a new X chromosome tumor suppressor gene. WTX is commonly inactivated in Wilms’ tumor.
WTX has also been shown to be somatically inactivated in 11-29% of cases of Wilms tumor.
Germline mutations in WTX cause an X-linked sclerosing bone dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS; MIM.300373). This condition is typically characterized by increased bone density and craniofacial malformations in females and lethality in males.
WTX (FAM123B) encodes a repressor of canonical WNT signaling.
Despite being germline for such mutations, individuals with OSCS are not predisposed to tumor development.
The observed phenotypic discordance dependent upon whether a mutation is germline or occurs somatically suggests the existence of temporal or spatial constraints on the action of WTX during tumorigenesis. (19079258)
WTX inactivation in sporadic Wilms tumor (MIM.194070) with tumoral deletions at chromosome Xq11.1
WTX inactivation by t(X;18)(q11;p11) with deletion of the WTX locus at Xq11. (17620295)
Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Jenkins ZA, van Kogelenberg M, Morgan T, Jeffs A, Fukuzawa R, Pearl E, Thaller C, Hing AV, Porteous ME, Garcia-Miñaur S, Bohring A, Lacombe D, Stewart F, Fiskerstrand T, Bindoff L, Berland S, Adès LC, Tchan M, David A, Wilson LC, Hennekam RC, Donnai D, Mansour S, Cormier-Daire V, Robertson SP. Nat Genet. 2009 Jan;41(1):95-100. PMID: 19079258
Han M, Rivera MN, Batten JM, Haber DA, Cin PD, Iafrate AJ. Wilms’ tumor with an apparently balanced translocation t(X;18) resulting in deletion of the WTX gene. Genes Chromosomes Cancer. 2007 Oct;46(10):909-13. PMID: 17620295
Major MB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C, Biechele TL, Gingras AC, Zheng N, Maccoss MJ, Angers S, Moon RT. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science. 2007 May 18;316(5827):1043-6. PMID: 17510365
Nusse R. Cancer. Converging on beta-catenin in Wilms tumor. Science. 2007 May 18;316(5827):988-9. PMID: 17510350
Bagchi S. New tumour suppressor linked to Wilms’ tumour. Lancet Oncol. 2007 Feb;8(2):102. No abstract available. PMID: 17290504
Rivera, M. N.; Kim, W. J.; Wells, J.; Driscoll, D. R.; Brannigan, B. W.; Han, M.; Kim, J. C.; Feinberg, A. P.; Gerald, W. L.; Vargas, S. O.; Chin, L.; Iafrate, A. J.; Bell, D. W.; Haber, D. A. : An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science 315: 642-645, 2007. PubMed ID : 17204608