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Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein β1 gene CTNNB1 for patients with Wilms tumors†

Results of long-term surveillance of 71 patients from International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology

  1. Brigitte Royer-Pokora PhD1,‡,*,
  2. Angela Weirich MD2,
  3. Valerie Schumacher PhD1,
  4. Constanze Uschkereit MS1,
  5. Manfred Beier BE1,
  6. Ivo Leuschner MD3,
  7. Norbert Graf MD4,
  8. Frank Autschbach MD5,
  9. Dominique Schneider MD6,
  10. Melissa von Harrach MS1

Article first published online: 10 JUL 2008

DOI: 10.1002/cncr.23672

Issue

Cancer

Cancer

Volume 113, Issue 5, pages 1080–1089, 1 September 2008

Additional Information

How to Cite

Royer-Pokora, B., Weirich, A., Schumacher, V., Uschkereit, C., Beier, M., Leuschner, I., Graf, N., Autschbach, F., Schneider, D. and von Harrach, M. (2008), Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein β1 gene CTNNB1 for patients with Wilms tumors. Cancer, 113: 1080–1089. doi: 10.1002/cncr.23672

Author Information

  1. 1

    Institute of Human Genetics and Anthropology, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany

  2. 2

    Department of Pediatric Hematology and Oncology, Children's Hospital, University of Heidelberg, Heidelberg, Germany

  3. 3

    Institute of Pediatric Pathology, University of Kiel, Kiel, Germany

  4. 4

    Department of Pediatric Hematology and Oncology, Children's Hospital, University of the Saarland, Homburg, Germany

  5. 5

    Department of General Pathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany

  6. 6

    Department of Pediatric Hematology and Oncology, Children's Hospital, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany

  1. ‡

    Fax: (011) 49 211 8112538;

*Institute of Human Genetics and Anthropology, Heinrich-Heine University of Duesseldorf, Postfach 101007, D40001 Duesseldorf, Germany

  1. †

    See editorial on pages 893-6, this issue.

Publication History

  1. Issue published online: 20 AUG 2008
  2. Article first published online: 10 JUL 2008
  3. Manuscript Accepted: 13 FEB 2008
  4. Manuscript Revised: 11 FEB 2008
  5. Manuscript Received: 10 OCT 2007

Funded by

  • Elterninitiative Kinderkrebsklinik e.V., Duesseldorf

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Keywords:

  • Wilms tumor;
  • long-term follow-up study;
  • WT1 mutations;
  • CTNNB1 mutations;
  • second tumor events;
  • bilateral disease

The authors studied the volumetric chemotherapy response in patients who had Wilms tumors (WT) with or without WT suppressor 1 gene (WT1) and with or without mutations in the cadherin-associated protein β1 gene (CTNNB1) and also examined long-term survival and second tumor events. The results indicated that patients with WT1 germline mutations have an increased risk for bilateral disease and second tumor events; therefore, tumor surveillance into adulthood should be considered.

Abstract

BACKGROUND.

Mutations in the Wilms tumor (WT) suppressor 1 gene (WT1) and the cadherin-associated protein β1 gene (CTNNB1) are found predominantly in stromal type WT, defining a genetic subgroup. The clinical relevance of these mutations remains to be determined.

METHODS.

A long-term follow-up study was performed for 71 patients (International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology; n = 77 tumors) with known molecular genetic status. Eight patients had bilateral disease, including 2 patients with a WT in both kidneys and 5 patients with a WT in 1 kidney and nephrogenic rests (NRs) in the other kidney. The response to preoperative chemotherapy, relapses, metastases, metachronous tumor development, and deaths were evaluated with a median follow-up of 12 years and 4 months.

RESULTS.

Nineteen patients (n = 24 tumors) had WT1 mutations, and 16 were constitutional mutations. Three patients with germline mutations had second tumor events: Two patients developed a WT in the kidney with NRs 3 years and 11 years after the first tumor; and 1 patient developed second tumors after 2 years, 1 in the kidney with a previous WT and 1 in the kidney with a previous NR. Eighteen of the WT1 mutant tumors were analyzed for CTNNB1 mutations, and all had mutations. A poor volumetric response (progression and <50% reduction) was observed in all patients who had tumors with a WT1 mutation and in 23 of 52 nonmutant tumors.

CONCLUSIONS.

Patients with WT1 germline mutations had an increased risk for bilateral disease and second tumor events. Therefore, the authors concluded that tumor surveillance until adulthood should be considered. Although tumors with both WT1 and CTNNB1 mutations had a poor volumetric response, there was no significant difference in overall survival in this cohort of patients with and without WT1 mutations. Cancer 2008. © 2008 American Cancer Society.

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