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 language | English |
|---|---|
| Pages (from-to) | 344-348 |
| Number of pages | 5 |
| Journal | Pediatric Blood and Cancer |
| Volume | 51 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2008 |
Fingerprint
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
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 journal › Article
}
TY - JOUR
T1 - Moleculaar evidence of the independent origin of multiple wilms tumors in a case of WAGR syndrome
AU - Uccini, Stefania
AU - Perotti, Daniela
AU - Colarossi, Cristina
AU - Stoppacciaro, Antonella
AU - Sardella, Michele
AU - Mannarino, Olga
AU - Collini, Paola
AU - Casieri, Paola
AU - Cozzi, Denis
AU - Amoroso, Loredana
AU - Spreafico, Filippo
AU - Radice, Paolo
AU - Dominici, Carlo
PY - 2008/9
Y1 - 2008/9
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.
KW - β-catenin
KW - WAGR syndrome
KW - Wilms tumor
KW - WT1 gene
UR - http://www.scopus.com/inward/record.url?scp=48249143175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48249143175&partnerID=8YFLogxK
U2 - 10.1002/pbc.21507
DO - 10.1002/pbc.21507
M3 - Article
VL - 51
SP - 344
EP - 348
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
SN - 1545-5009
IS - 3
ER -