Molecular and cellular heterogeneity of wilms' tumor

Llamas‐Velasco, Sara; D’Amico, Domenico; Schneider, Nancy R.; Timmons, Charles F.; Chappell, Elizabeth; Lee, Daniel; Nisen, Perry D.

doi:10.1002/ijc.2910530425

Cited by 16 publications

(8 citation statements)

References 13 publications

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“…In order to determine if chromosome 12 duplications or amplifications are involved in cyclin D2 and/or CDK4 overexpression, we are currently studying 60 tumors for chromosome 12 abnormalities. Previous studies, looking for RB LOH in WT, indicated the lack of involvement of this tumor suppressor gene in WT [45,46]. However, if the increased level of cyclin D2 and CDK4 message produces more of their protein complexes, then RB-mediated G1-phase arrest may be inhibited.…”

Section: Discussionmentioning

confidence: 94%

Profiling of differential gene expression in Wilms tumor by cDNA expression array

Rigolet

Faussillon

Baudry

et al. 2001

Pediatric Nephrology

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In order to identify genes or pathways involved in Wilms tumor etiology, we used the Atlas Cancer cDNA expression array to compare the gene expression profiles of five tumors, one Wilms tumor cell line (SK-NEP1), and normal mature and fetal kidneys. Of 588 genes tested, 153 had a different expression pattern in tumors compared with mature kidney. Ninety-six genes were differentially expressed in tumors compared with both normal mature and fetal kidney, and 57 genes had expression profiles similar to that of fetal kidney, which may reflect the developmental stage of the tumor cells. Comparison of the expression patterns of tumors shows that only 13% of the differentially expressed genes are constantly up- or downregulated in the five tumors tested, and this provides molecular evidence of tumor heterogeneity. We then confirmed the differential expression by an independent method, using quantitative reverse transcriptase polymerase chain reaction for two of the differentially expressed genes, MMP-14 and cyclin D2. Analysis of expression levels in a panel of 40 tumors showed that 30% overexpressed MMP-14 and 80% overexpressed cyclin D2. Profiling of gene expression using cDNA arrays in a large tumor panel will ultimately lead to the molecular classification of tumors, the identification of prognosis markers, and the design of targeted therapy.

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Section: Discussionmentioning

confidence: 94%

Profiling of differential gene expression in Wilms tumor by cDNA expression array

Rigolet

Faussillon

Baudry

et al. 2001

Pediatric Nephrology

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“…The most widely investigated is the WTI gene, which is mapped to Ip 13. The p53 gene has also been suggested to play a role in the pathogenesis of nephroblastomas (Lemoine et al, 1992;Velasco et al, 1993). This study looked at the prognostic significance of the immunohistochemical detection of p53 protein in nephroblastomas.…”

Section: Discussionmentioning

confidence: 99%

p53 protein expression in nephroblastomas: a predictor of poor prognosis

Govender

Harilal²,

Hadley³

et al. 1998

Br J Cancer

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Summary Alteration of the tumour-suppressor gene p53 is the commonest genetic change encountered in human malignant tumours. A study was undertaken to ascertain the prognostic value of p53 immunoexpression in nephroblastomas. A series of 93 consecutive cases was analysed. Archival formalin-fixed, paraffin wax-embedded tissue sections were stained with monoclonal anti-p53 antibody (DO-7, Dako) using a peroxidase-labelled streptavidin biotin kit. Five of seven tumours (71.4%) with unfavourable histology, but only 3 of 86 favourable histology tumours, showed 'high' p53 immunoexpression (P < 0.001). p53 expression in unfavourable histology tumours was present in both anaplastic and non-anaplastic components. Moreover, there was uniform staining of blastema, epithelium and stroma in unfavourable histology tumours. No statistical difference in p53 expression was found between patients who had received and those who had not received preoperative chemotherapy (P = 0.678). Similarly, no statistical difference was found in the groups of patients who were disease free, who had residual/recurrent disease or who had died (P = 0.238). The mean survival period for patients with tumours that had 'low' and 'high' expressions was 24.8 months and 12.6 months respectively (P = 0.0003). In conclusion, p53 immunoexpression in nephroblastomas was found to be an important determinant of poor prognosis as it identifies those patients with a shorter survival period and also those with unfavourable histology tumours. It may also be of practical value to the practising pathologist by identifying those tumours that require careful assessment for the presence of anaplasia.

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“…Although the Wilms' tumour suppressor gene (WT1), mapped within chromosome 11p13 18,19 , is the best known anti-oncogene associated with Wilms' tumour, p53 mutations 11,13 have occasionally been implicated in the pathogenesis of Wilms' tumour. The concept of multiple sites of genetic 'hits', besides 11p13, seems feasible in the evolution of Wilms' tumour as cytogenetic studies have identified aberrations within 11p15 and 16q in some cases 20,21 .…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of p53 alterations in paediatric tumours is however less well established. Conflicting reports regarding the possible existence of p53 mutations in Wilms' tumour (nephroblastoma) have emerged from various studies [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of p53 proteins in Wilms’ tumour: a possible association with the histological prognostic parameter of anaplasia

Cheah¹,

Looi²,

Chan

1996

Histopathology

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Wilms' tumour (nephroblastoma) has been associated with chromosomal abnormalities at the 11p13, 11p15 and 16q regions. A study into the possibility of mutations occurring within p53, the ubiquitous adult tumour suppressor gene, in Wilms' tumour was carried out. Thirty-eight cases were studied. Of these 36 were categorised into the favourable histology group and two into the unfavourable histology group based on the National Wilms' Tumour Study criteria. Archival formalin-fixed, paraffin-embedded tissue sections from each case were stained with a polyclonal (AB565:Chemicon) and a monoclonal (DO7:Dako) antibody raised against p53 protein using a peroxidase-labelled streptavidin biotin kit (Dako). 'Cure' (disease-free survival of 60 months or longer) was documented in 39% of cases with favourable histology tumours. Eleven percent in this group succumbed to the disease. Both cases with unfavourable histology died. Four out of 36 (11%) tumours with favourable histology demonstrated weak to moderate staining with both AB565 and DO7 in more than 75% of tumour cells. In contrast, p53 protein expression in unfavourable histology tumours was significantly increased compared with the favourable histology group (P = 0.021) with both cases demonstrating immunopositivity in > 75% of tumour cells when stained with AB565 and DO7. The intensity of staining ranged from moderate to strong in both cases. It appears from this preliminary study that the immunohistochemical expression of p53 protein in Wilms' tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms' tumours.

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Molecular and cellular heterogeneity of wilms' tumor

Cited by 16 publications

References 13 publications

Profiling of differential gene expression in Wilms tumor by cDNA expression array

Profiling of differential gene expression in Wilms tumor by cDNA expression array

p53 protein expression in nephroblastomas: a predictor of poor prognosis

Immunohistochemical expression of p53 proteins in Wilms’ tumour: a possible association with the histological prognostic parameter of anaplasia

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