This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Little, S. E. Articles by Pritchard-Jones, K. Search for Related Content PubMed PubMed Citation Articles by Little, S. E. Articles by Pritchard-Jones, K. Social Bookmarking                            What's this?

Frequency and Heritability of WT1 Mutations in Nonsyndromic Wilms' Tumor Patients: A UK Children’s Cancer Study Group Study

From the Sections of Paediatric Oncology and Cancer Genetics, Institute of Cancer Research, Royal Marsden Hospital; and Paediatric Oncology Unit, The Royal Marsden Hospital, Sutton, Surrey, United Kingdom

Address reprint requests to Kathy Pritchard-Jones, MD, Paediatric Oncology Unit, The Royal Marsden NHS Trust, Downs Rd, Sutton, Surrey, SM2 5PT United Kingdom; e-mail: Kathy.Pritchard-Jones{at}icr.ac.uk

PURPOSE: Constitutional WT1 mutations in patients with Wilms' tumor (WT) have specifically been associated with genitourinary abnormalities, such as cryptorchidism and hypospadias. We sought to ascertain the frequency and heritability of constitutional WT1 mutations in nonsyndromic WT patients.

PATIENTS AND METHODS: Constitutional DNA from 282 patients treated at seven United Kingdom Children's Cancer Study Group centers was screened for WT1 mutations using heteroduplex analysis. Bidirectional sequencing was used to confirm the mutation and to analyze the corresponding parental DNA samples.

RESULTS: Five different constitutional WT1 mutations were identified in six children. Mutations in four patients were confirmed to be de novo, and all five mutations are predicted to produce truncated protein. The WT1 mutation group had a young median age at diagnosis of 13.8 months, compared with 34.9 months in the group in whom no WT1 mutations were found; four were female and two were male; and all tumors were of favorable histology. The three tumors with known histologic subtype were stromal-predominant. Contrary to expectation, four of six mutations occurred in children with unilateral tumors without any associated genitourinary abnormality.

CONCLUSION: Constitutional WT1 mutations occur with a low frequency (2.1%; 95% CI, 0.8% to 4.6%) in nonsyndromic WT patients. Most mutations occurred in children with unilateral WT without associated genitourinary abnormalities, creating difficulties in identifying individuals with germline mutations on phenotype alone. Two factors that may indicate that an individual is carrying a germline WT1 mutation are an early age of onset and stromal-predominant histology of the WT.

Supported in part by Cancer Research UK.

Presented as platform presentations at British Cancer Research Meeting, Bournemouth, UK, July 2-5, 2003, and 35th Congress of the International Society of Paediatric Oncology, Cairo, Egypt, October 8-11, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				V. I. Gaidzik, R. F. Schlenk, S. Moschny, A. Becker, L. Bullinger, A. Corbacioglu, J. Krauter, B. Schlegelberger, A. Ganser, H. Dohner, et al. Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group Blood, May 7, 2009; 113(19): 4505 - 4511. [Abstract] [Full Text] [PDF]

				R H Scott, C A Stiller, L Walker, and N Rahman Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour J. Med. Genet., September 1, 2006; 43(9): 705 - 715. [Abstract] [Full Text] [PDF]