Moleculaar evidence of the independent origin of multiple wilms tumors in a case of WAGR syndrome

Stefania Uccini, Daniela Perotti, Cristina Colarossi, Antonella Stoppacciaro, Michele Sardella, Olga Mannarino, Paola Collini, Paola Casieri, Denis Cozzi, Loredana Amoroso, Filippo Spreafico, Paolo Radice, Carlo Dominici

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Abstract

Background. This study investigated the genetic events leading to tumorigenesis in a patient affected with WAGR syndrome who developed multiple distinct Wilms tumors (WTs). Procedure and Results. At 1 year of age, the child developed two synchronous bilateral WTs that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while β-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular investigations of WT1 gene and exon 3 of β-catenin (CTNNB1) gene detected no mutations. At 4 years of age, 28 months after the chemotherapy completion, a third WT was diagnosed in the left kidney, and surgically removed before any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while β-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular analysis of the third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene, leading to a frameshift of the reading frame and to a premature stop of the translation (c.925_928delACTC, p.T309LfsX71); no mutations in the exon 3 of the β-catenin gene were documented. Conclusions. These data demonstrate that multiple WTs can arise as a consequence of different genetic events in a patient with genetic predisposition, such as WAGR syndrome.

Original languageEnglish
Pages (from-to)344-348
Number of pages5
JournalPediatric Blood and Cancer
Volume51
Issue number3
DOIs
Publication statusPublished - Sep 2008

Fingerprint

WAGR Syndrome
Wilms Tumor
Catenins
Exons
Neoplasms
Neoplasm Metastasis
Kidney
Lung
Genes
Drug Therapy
Reading Frames
Mutation
Genetic Predisposition to Disease
Nephrectomy
Carcinogenesis
Proteins
Immunohistochemistry

Keywords

  • β-catenin
  • WAGR syndrome
  • Wilms tumor
  • WT1 gene

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Medicine(all)

Cite this

Uccini, S., Perotti, D., Colarossi, C., Stoppacciaro, A., Sardella, M., Mannarino, O., ... Dominici, C. (2008). Moleculaar evidence of the independent origin of multiple wilms tumors in a case of WAGR syndrome. Pediatric Blood and Cancer, 51(3), 344-348. https://doi.org/10.1002/pbc.21507

Moleculaar evidence of the independent origin of multiple wilms tumors in a case of WAGR syndrome. / Uccini, Stefania; Perotti, Daniela; Colarossi, Cristina; Stoppacciaro, Antonella; Sardella, Michele; Mannarino, Olga; Collini, Paola; Casieri, Paola; Cozzi, Denis; Amoroso, Loredana; Spreafico, Filippo; Radice, Paolo; Dominici, Carlo.

In: Pediatric Blood and Cancer, Vol. 51, No. 3, 09.2008, p. 344-348.

Research output: Contribution to journalArticle

Uccini, S, Perotti, D, Colarossi, C, Stoppacciaro, A, Sardella, M, Mannarino, O, Collini, P, Casieri, P, Cozzi, D, Amoroso, L, Spreafico, F, Radice, P & Dominici, C 2008, 'Moleculaar evidence of the independent origin of multiple wilms tumors in a case of WAGR syndrome', Pediatric Blood and Cancer, vol. 51, no. 3, pp. 344-348. https://doi.org/10.1002/pbc.21507
Uccini, Stefania ; Perotti, Daniela ; Colarossi, Cristina ; Stoppacciaro, Antonella ; Sardella, Michele ; Mannarino, Olga ; Collini, Paola ; Casieri, Paola ; Cozzi, Denis ; Amoroso, Loredana ; Spreafico, Filippo ; Radice, Paolo ; Dominici, Carlo. / Moleculaar evidence of the independent origin of multiple wilms tumors in a case of WAGR syndrome. In: Pediatric Blood and Cancer. 2008 ; Vol. 51, No. 3. pp. 344-348.
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N2 - Background. This study investigated the genetic events leading to tumorigenesis in a patient affected with WAGR syndrome who developed multiple distinct Wilms tumors (WTs). Procedure and Results. At 1 year of age, the child developed two synchronous bilateral WTs that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while β-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular investigations of WT1 gene and exon 3 of β-catenin (CTNNB1) gene detected no mutations. At 4 years of age, 28 months after the chemotherapy completion, a third WT was diagnosed in the left kidney, and surgically removed before any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while β-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular analysis of the third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene, leading to a frameshift of the reading frame and to a premature stop of the translation (c.925_928delACTC, p.T309LfsX71); no mutations in the exon 3 of the β-catenin gene were documented. Conclusions. These data demonstrate that multiple WTs can arise as a consequence of different genetic events in a patient with genetic predisposition, such as WAGR syndrome.

AB - Background. This study investigated the genetic events leading to tumorigenesis in a patient affected with WAGR syndrome who developed multiple distinct Wilms tumors (WTs). Procedure and Results. At 1 year of age, the child developed two synchronous bilateral WTs that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while β-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular investigations of WT1 gene and exon 3 of β-catenin (CTNNB1) gene detected no mutations. At 4 years of age, 28 months after the chemotherapy completion, a third WT was diagnosed in the left kidney, and surgically removed before any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while β-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular analysis of the third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene, leading to a frameshift of the reading frame and to a premature stop of the translation (c.925_928delACTC, p.T309LfsX71); no mutations in the exon 3 of the β-catenin gene were documented. Conclusions. These data demonstrate that multiple WTs can arise as a consequence of different genetic events in a patient with genetic predisposition, such as WAGR syndrome.

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