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FAM123B

Monday 18 June 2007

WTX (or FAM123B) is a new X chromosome tumor suppressor gene. WTX is commonly inactivated in Wilms’ tumor.

Abnormalities in WNT signaling are implicated in a broad range of developmental anomalies and also in tumorigenesis.

Pathology

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.

The mouse homolog of WTX is expressed in the fetal skeleton, and alternative splicing implicates plasma membrane localization of WTX as a factor associated with survival in males with OSCS.

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#)

References

- 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#

- Huff V. Wilms tumor genetics: a new, UnX-pected twist to the story. Cancer Cell. 2007 Feb;11(2):105-7. PMID: #17292822#

- 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#