RT Journal Article SR Electronic T1 WTX mutations can occur both early and late in the pathogenesis of Wilms tumour JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 791 OP 794 DO 10.1136/jmg.2010.080663 VO 47 IS 11 A1 Ryuji Fukuzawa A1 Sarah K Holman A1 C W Chow A1 Ravi Savarirayan A1 Anthony E Reeve A1 Stephen P Robertson YR 2010 UL http://jmg.bmj.com/content/47/11/791.abstract AB Background Somatic mutations in the X-linked tumour suppressor gene WTX have been observed in 6– 30% of sporadic cases of Wilms tumour. Germline mutations in the same gene cause the sclerosing skeletal dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS). No evidence points towards a susceptibility to the development of tumours in individuals with OSCS, suggesting that there are unrecognised additional determinants that influence the phenotypic outcome associated with germline mutations in WTX. One explanation may be that a somatic mutation in WTX may need to occur late in tumour development to contribute to tumourigenesis.Methods Here a panel of four sporadic Wilms tumours with associated nephrogenic rest tissue and characterised WTX and CTNNB1 mutations is studied to ascertain the temporal sequence of acquisition of these mutations. Additionally, a family with OSCS is described segregating a germline mutation in WTX and manifesting a lethal phenotype in males. One male from this family had bilateral multifocal nephrogenic rests at autopsy.Results In one of the four tumours the WTX mutation was present in both tumour and rest tissue indicating it had arisen early in tumour development. In the remaining three tumours, the WTX mutation was present in the tumour only indicating late acquisition of these mutations.Conclusions These data indicate that WTX mutations can arise both early and late in Wilms tumour development. WTX mutations may predispose to nephrogenic rest development rather than Wilms tumour per se.