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NCI CANCERLIT^® Search: Wilms| Tumor Gene (WT1) - September 2001

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Last Modified: November 1, 2001

• Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia.

• Fluorescent 5'-exonuclease assay for the absolute quantification of Wilms' tumour gene (WT1) mRNA: implications for monitoring human leukaemias.

• Life, sex, and WT1 isoforms--three amino acids can make all the difference.

CancerMail from the National Cancer InstituteWilms' Tumor Gene (WT1) - September 2001

1
UI - 21372067
AU - Gronskov K; Olsen JH; Sand A; Pedersen W; Carlsen N; Bak Jylling AM; Lyngbye T; Brondum-Nielsen K; Rosenberg T
TI - Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia.
SO - Hum Genet 2001 Jul;109(1):11-8
AD - Department of Medical Genetics, The John F. Kennedy Institute, Gl. Landevej 7, DK2600 Glostrup, Denmark. kag@kennedy.dk
Aniridia is a severe eye disease characterized by iris hypoplasia; both sporadic cases and familial cases with an autosomal dominant inheritance exist. Mutations in the PAX6 gene have been shown to be the genetic cause of the disease. Some of the sporadic cases are caused by large chromosomal deletions, some of which also include the Wilms tumor gene (WAGR syndrome), resulting in an increased risk of developing Wilms tumor. Based on the unique registration of both cancer and aniridia cases in Denmark, we have made the most accurate risk estimate to date for Wilms tumor in sporadic aniridia. We have found that patients with sporadic aniridia have a relative risk of 67 (confidence interval: 8.1-241) of developing Wilms tumor. Among patients investigated for mutations, Wilms tumor developed in only two patients out of 5 with the Wilms tumor gene (WT1) deleted. None of the patients with smaller chromosomal deletions or intragenic mutations were found to develop Wilms tumor. Our observations suggest a smaller risk for Wilms tumor than previous estimates, and that tumor development requires deletion of WT1. We report a strategy for the mutational analysis of aniridia cases resulting in the detection of mutations in 68% of sporadic cases and 89% of familial cases. We also report four novel mutations in PAX6, and furthermore, we have discovered a new alternatively spliced form of PAX6.

2
UI - 21421104
AU - Kreuzer KA; Saborowski A; Lupberger J; Appelt C; Na IK; le Coutre P; Schmidt CA
TI - Fluorescent 5'-exonuclease assay for the absolute quantification of Wilms' tumour gene (WT1) mRNA: implications for monitoring human leukaemias.
SO - Br J Haematol 2001 Aug;114(2):313-8
AD - Klinik und Poliklinik fur Innere Medizin m.S. Hamatologie und Onkologie, Campus Virchow-Klinikum, Medizinische Fakultat Charite der Humboldt-Universitat zu Berlin, Germany.
The Wilms' tumour gene (WT1) has been suggested as a powerful parameter for molecular monitoring of minimal residual disease (MRD) in leukaemias. However, molecular monitoring via WT1 RNA levels is far from being routinely performed, which is possibly owing to the complex and inaccurate quantitative reverse transcription polymerase chain reaction (RT-PCR) procedures. Using a newly-developed quantitative real time RT-PCR, we measured WT1 transcripts in peripheral blood leucocytes of patients with acute myeloid (AML), acute lymphoid (ALL) and chronic myeloid leukaemia (CML). While healthy blood donors did not show measurable amounts of WT1 transcripts, WT1 RNA levels were detectable in all types of leukaemia. Furthermore, intraindividual WT1 transcript kinetics were exclusively dependent on disease progression, treatment and subsequent disease outcome. Using this approach, we could distinguish between treatment response and failure within the first days of therapeutic intervention. Moreover, gradually rising WT1 levels over a period of weeks and months paralleled long-term disease progression and appeared to be a prognostic indicator for subsequent clinical relapse. A linear correlation between quantities of WT1 and bcr/abl fusion transcripts could be seen in CML. We conclude that quantitative assessment of WT1 transcripts using real-time PCR is an appropriate method for molecular monitoring of AML, ALL and CML, and can be used independently for both short- and long-term monitoring of leukaemia patients.

3
UI - 21417133
AU - Hastie ND
TI - Life, sex, and WT1 isoforms--three amino acids can make all the difference.
SO - Cell 2001 Aug 24;106(4):391-4
AD - MRC Human Genetics Unit, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, United Kingdom. nick.hastie@hgu.mrc.ac.uk