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Clinical Cancer Research Vol. 11, 4382-4387, June 15, 2005
© 2005 American Association for Cancer Research

Imaging, Diagnosis, Prognosis

Effects of Chemotherapy on the Cytogenetic Constitution of Wilms' Tumor

Thorsten Schlomm1, Bastian Gunawan2, Hans-Jürgen Schulten2, Björn Sander2, Karthinathan Thangavelu3, Norbert Graf5, Ivo Leuschner6, Rolf-Hermann Ringert4 and László Füzesi2

Authors' Affiliations: 1 Department of Urology, University of Hamburg-Eppendorf, Hamburg, Germany; Departments of 2 Pathology, 3 Medical Statistics, and 4 Urology, University of Göttingen, Göttingen, Germany; 5 Department of Pediatric Oncology, University of Homburg/Saar, Homburg/Saar, Germany; and 6 Department of Pediatric Pathology, University of Kiel, Kiel, Germany

Requests for reprints: László Füzesi, Department of Pathology, University of Göttingen, Robert-Koch-Strasse 40, D-37099 Göttingen, Germany. Phone: 49-551-396858; Fax: 49-551-398627; E-mail: fuezesi{at}med.uni-goettingen.de.


   Abstract
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 Abstract
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The management of Wilms' tumors consists of a combination of surgery, chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk stratified according to histologic subtype and stage. Although the cytogenetic characteristics of Wilms' tumors are well established, the cytogenetic effects related to chemotherapy are widely unknown. We herein report on comparative genomic hybridization findings in 41 primary Wilms' tumors of blastemal type, of which 19 had received preoperative chemotherapy (PCT group) and 22 did not (non-PCT group). Overall, imbalances could be detected in 32 tumors, with +1q (17 cases), +7q (10 cases), +7p (6 cases), and –7p (6 cases) as the most common changes. Among these, +7q and –7p were both significantly associated with metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively), and +7q was also associated with higher stage (stages III + IV; P = 0.003). There were significant differences in the cytogenetic constitution of tumors between the two treatment groups. As a trend, tumors in the preoperative-chemotheraphy group had fewer changes (mean, 2.7) than those in the non-preoperative-chemotheraphy group (mean, 3.8), and the frequencies of imbalances at 7p or +7q, respectively, were significantly lower compared with tumors in the non-preoperative-chemotheraphy group (2 of 19 versus 10 of 22, P = 0.019; 1 of 19 versus 9 of 22, P = 0.011). In contrast, –1q was common in both the preop-CT group (10 of 19) and the non-preop-CT group (7 of 22). The results suggest that Wilms' tumor clones with +1q are not obliterated by preoperative chemotherapy, whereas cytogenetically more complex clones with +7q and/or imbalances at 7p seem more responsive and are more likely to be eliminated by chemotherapeutic treatment.

Key Words: Pediatric cancers • Molecular cytogenetics

Wilms' tumor, or nephroblastoma, is the most common renal neoplasm of childhood with overall long-term survival rates approaching 90% in localized disease and over 70% for metastatic disease using current therapeutic protocols created by the International Society of Pediatric Oncology (SIOP) or the National Wilms' Tumor Study Group (1). The SIOP protocols advocate preoperative chemotherapy followed by surgery and postoperative treatment which is stratified according to histologic evidence of responsiveness to preoperative therapy, as reflected by post-therapy classification (low-risk, intermediate-risk, and high-risk histology; refs. 2–8). Although the vast majority of children with Wilms' tumor, particularly of blastemal type, respond well to standardized therapy, a small proportion of patients show nonresponsiveness to chemotherapy. In these cases, extensive residual blastemal tumor cells are frequently found following pretreatment. It seems that in addition to anaplasia as a well-established predictive factor for poor responsiveness to chemotherapy, the persistence of large amounts of viable blastemal cells is also related to low response and reduced prognosis requiring intensified therapy. On the other hand, large amounts of necrosis and/or maturation into differentiated components are considered as evidence for responsiveness and may confer a more favorable prognosis (1, 7, 9). The current SIOP/GPOH 2001 trial is designed to tailor treatment by stratifying patients considering individual clinicopathologic factors to minimize potentially nephrotoxic and cardiotoxic side effects of chemotherapeutic agents. Other biological variables that may eventually allow greater ability to stratify patients may derive from investigations focusing on drug resistance–related proteins (10–13). Recently, cDNA microarray studies suggest that low-stage Wilms' tumors with a good response to chemotherapy are characterized by high expression of genes encoding for topoisomerase IIa, stathmin I, and tubulin (14).

Molecular and cytogenetic studies have found recurrent allelic losses and chromosomal imbalances in Wilms' tumors and some markers were implicated to correlate with clinicopathologic factors (15–18). The closed nonrandomized NWTS-5 trial showed a prognostic value for loss of heterozygosity at chromosomes 1p and 16q and DNA ploidy (19). However, the cytogenetic changes induced by chemotherapy are widely unknown. The aim of the present study was to assess possible effects of preoperative chemotherapy on the molecular cytogenetic constitution of Wilms' tumors.


   Materials and Methods
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Tumor samples. For the study, tumor samples from 41 primary Wilms' tumor specimens were recruited from the Kiel Paediatric Tumor Registry of the German Society of Paediatric Oncology and Hematology (GPOH) at the Department of Paediatric Pathology, University of Kiel. Medical records were obtained from the German Wilms' Tumor Study Group. Only tumors with blastemal predominant histology as defined by Beckwith and Palmer (20) without anaplasia were included in the study. From the GPOH database, 19 patients that had received preoperative chemotherapy before surgery and adjuvant therapy were selected randomly from among a larger pool of cases for the preoperative chemotherapy group (PCT group). For control, all 22 patients treated by up front surgery followed by adjuvant therapy and with samples available were included for the nonpreoperative chemotherapy group (non-PCT group). Tumor stage was classified at the time of surgery according to the SIOP.

DNA extraction. Genomic tumor DNA was extracted from formalin-fixed and paraffin-embedded tissue specimens. Corresponding H&E-stained slides served as templates to isolate only nonnecrotic blastemal tumor components by microdissection. Collected material was deparaffinized by three consecutive wash procedures at 95°C in 1 mL buffer solution [10 mmol/L Tris (pH 8.3), 50 mmol/L KCl, 1.5 mmol/L MgCl2]. The samples were then treated with proteinase K (1 mg/mL final concentration; Roche, Mannheim, Germany) and further processed using spin columns according to the manufacturer's protocol (Qiagen, Hilden, Germany).

Comparative genomic hybridization analysis. All comparative genomic hybridization (CGH) experiments were done essentially as described previously (21). Tumor DNA was labeled with biotin-16-dUTP (Roche) and normal reference DNA with digoxigenin-11-dUTP (Roche) by means of standard nick translation. The denatured DNA probes containing each 2 µg of tumor DNA, 1.5 µg of reference DNA, and 80 µg of COT-1 DNA were hybridized for 3 days to normal metaphase spreads (Vysis, Downers Grove, IL). Subsequently, the slides were washed extensively, blocked with bovine serum albumin solution, and incubated with fluorescein-conjugated avidin (Vector Laboratories, Burlingame, CA) and rhodamine-conjugated antidigoxigenin (Roche). Finally, the slides were washed again and mounted in antifade solution (Vector Laboratories) containing 1.25 µg/mL of 4',6-diamidino-2-phenylindole counterstain. Image acquisition was done on a Zeiss Axioskop fluorescence microscope (Zeiss, Göttingen, Germany) equipped with three separate bandpass filters (4',6-diamidino-2-phenylindole, green and red spectrum) and a highly sensitive monochrome charge-coupled device camera (Photometrics, Tucson, AZ). For each analysis, the averaged chromosome-specific green to red fluorescence ratios from at least 10 well-selected metaphases were plotted using the Quips CGH software (distributed through Applied Imaging, Newcastle, United Kingdom). Relative copy number changes were interpreted as gains when the average green-to-red ratio exceeded 1.2, and as losses when the corresponding ratio was <0.8. Exceptionally, in a few cases with only trends reaching not the aforementioned thresholds, deviations from normal were classified as gains or losses when the plotted 95 % confidence interval varied beyond the ratio of 1.0 and simultaneously, the ratio exceeded 1.15 or was <0.85. Chromosomal regions 1p32pter, 13p, 14p, 15p, 19, 21p, 22p, Y, telomeres, and constitutive heterochromatic regions at 1q, 9q, and 16q, reported to produce false results by CGH were excluded from all analyses (22, 23).

Statistical analysis. For statistical analyses, DNA copy number changes were expressed as imbalances (losses and gains) for p-arms and q-arms of metacentric and submetacentric chromosomes, and q-arms of acrocentric chromosomes, respectively. Differences in the frequencies of individual imbalances between the two treatment groups and associations between tumor stage (SIOP stages I + II versus III + IV) or metastatic disease at the time of surgery and individual imbalances were evaluated using the two-sided Fisher's exact test. Because the analysis was of an exploratory nature, no adjustment for multiple testing was done. The significance level was 5%. All statistical analyses were done using the software system R (http://www.r-project.org/).


   Results
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Clinicopathologic data. The clinicopathologic data of all patients are summarized in Table 1. The female-to-male ratio was 16:6 in the non-PCT group and 13:6 in the preoperative-chemotheraphy group. Mean age at diagnosis was 7.1 years in the non-PCT group (range, birth to 32 years) and 5.7 years in the PCT group (range, 9 months to 17 years), and mean follow-up time was 4.3 years in the non-PCT group (range, 9 months to 9 years), and 4.0 years in the PCT group (range, 18 months to 7.3 years). Tumor stage was significantly higher among the 22 cases in the non-PCT group compared with the 19 cases in the PCT group (stages I + II: 11 versus 17; stages III + IV: 11 versus 1; P = 0.004). Among 16 patients, where effect of chemotherapy was clinically evaluated, 14 patients responded to chemotherapy with reduction of tumor volume, whereas two patients developed increase of tumor volume (data not shown). In both groups, all patients except one received postoperative chemotherapy combined with radiotherapy in 12 cases. One of six patients in the non-PCT group and all four patients in the PCT group that developed tumor relapse have died of disease during follow-up.


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  		Table 1. Clinicopathologic and CGH findings in 41 primary Wilms' tumors with and without preoperative chemotherapy

 
Comparative genomic hybridization analysis. Genomic imbalances were detected in 18 of 22 (82%) tumors of the non-PCT group and 14 of 19 (74%) tumors of the PCT group (Table 1; Fig. 1). Overall, the most frequent individual imbalances were +1q (17 cases), +7q (10 cases), +7p (6 cases), –7p (6 cases), –1p (6 cases), +12p (5 cases), +12q (5 cases), +8q (5 cases), +18p, (5 cases), and +18q (5 cases). Among these, +7q and –7p were both significantly associated with metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively). Moreover, +7q, +12p, and +12q were associated with higher stage (stages III + IV; P = 0.003, P = 0.02, and P = 0.02, respectively). Losses at 11p including the Beckwith-Wiedemann and the WT-1 gene loci at 11p13 were observed in four cases (cases 3, 13, 39, and 41).



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  		Fig. 1. Overview of chromosomal imbalances in 22 Wilms' tumors without (A) and 19 Wilms' tumors with preoperative chemotherapy (B). Losses (bars, left) and gains (bars, right). Euchromatin regions excluded from analysis (gray boxes).

 
When comparing tumors with and without preoperative chemotherapy, tumors in the non-PCT group had on average more changes (mean, 3.8) than tumors in the PCT group (mean, 2.7). As a trend, gains predominated over losses in both the non-PCT group (2.8 versus 1.0) and the PCT group (1.6 versus 1.1).

In the non-PCT group, the most prevalent imbalances were +7q (9 of 22), +1q (7 of 22), +7p (5 of 22), and –7p (5 of 22). In four cases (cases 5, 8, 17, and 20), +7q was associated with simultaneous –7p, suggesting an isochromosome of the long arm of chromosome 7 as underlying cytogenetic aberration.

In the PCT group, +1q (10 of 19) was by far the most common imbalance, whereas +7q (1 of 19), +7p (1 of 19), and –7p (1 of 19) were only revealed to be nonrecurrent events. Thus, whereas +1q remained a prevalent imbalance and even was detected at an increased frequency compared with tumors without preoperative chemotherapy, the frequencies of +7q or imbalances at 7p were significantly lower (P = 0.011 and P = 0.019, respectively), leading to cytogenetically less complex karyotypes with overall fewer imbalances.

Among relapsed patients, there seemed some differences in event-free survival (EFS) for chromosome 7 imbalances. In the non-PCT group, four patients had synchronous distant metastases (mean EFS, 0 months) and these patients were disclosed to have tumors with +7q. Another two patients without chromosome 7 changes in their tumors only developed relapse during follow-up, either regional lymph node metastasis (EFS, 34 months) or local recurrence (EFS, 4 months). In the PCT group, the four relapsed patients were disclosed to have tumors without chromosome 7 abnormalities, and these patients only developed metastatic disease in the setting of local recurrence. EFS for these patients was 10, 12, 12, and 21 months, respectively. Losses at 16q were observed at lower frequencies (overall 3 of 41). However, both patients in the PCT group with loss of 16q have died of disease.


   Discussion
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 Materials and Methods
 Results
 Discussion
References
 
The cytogenetics of Wilms' tumors has been studied extensively. Chromosomal aberrations that have been identified in these tumors include gains at 1q, 6, 7q, 8, 12, and 17q and losses at 1p, 7p, 11q, 16q, and 22q (17, 24–32). The first study to use comparative genomic hybridization for the analysis of eight familial Wilms' tumors described common gains on chromosomes 6, 8, and 12 and frequent chromosomal losses at 3q, 4q, 9p, 16q, and 20p (33). Later studies identified gains at 1q as the most prevalent change in Wilms' tumors, followed by gains at 7q and losses at 7p (34, 35). Hing et al. (16) identified high frequencies of gains at 1q in relapsed tumors. However, the effects of chemotherapy on the cytogenetic constitution of these tumors are widely unknown.

This study presents the first data on CGH analysis in primary Wilms' tumors showing differences between tumors with and without preoperative chemotherapy. We could show that high frequencies of +1q seemed maintained in pretreated tumors, whereas imbalances involving chromosome 7, i.e. +7q, +7p, and –7p, were significantly less common after chemotherapeutic treatment, contributing to simpler karyotypes with fewer cytogenetic changes. Steenman et al. (35) investigated 46 Wilms' tumors and six cases of nephroblastomatosis after preoperative chemotherapy and identified +7q in comparably low frequencies of 9% compared with +1q or +12q in 20% of their tumors. These observations suggest that Wilms' tumor clones with +1q apparently are not obliterated by chemotherapeutic treatment, in line with a concept that clones with +1q are less responsive to chemotherapeutic treatment and therefore may be detected at a somewhat increased frequency in pretreated tumors. This would also explain previously published data indicating a high incidence of 1q gains in relapsed Wilms' tumors of otherwise favorable histology (16). It may also be speculated whether chromosomal gains at 1q are related to drug resistance as is being considered in other tumors (e.g. ovarian cancers and neuroblastoma, respectively; ref. 36).

On the other hand, cytogenetically more complex clones with +7q and/or imbalances at 7p seemed obliterated by chemotherapy resulting in low frequencies of clones with chromosome 7 imbalances in pretreated tumors. One explanation for this observation would be that chromosome 7 imbalances rather represent secondary changes associated with increased karyotypic instability and presumably a higher potential for accelerated growth, making these clones more susceptible to chemotherapeutic treatment. This concept is also supported by the present observation that chromosome 7 imbalances seemed associated with higher tumor stage. Considering the imbalanced distribution of stage IV tumors between the two groups in the present series, we cannot rule out that the observed differences in frequencies of +7q may also reflect to a certain extent a covariation with stage. However, previous studies that were done largely on pretreated specimens also reveal lower incidences of +7q compared with those of +1q (24, 26, 35). Alternatively, it would seem equally likely that chromosome 7 changes may characterize a distinct cytogenetic subset of Wilms' tumor and that those tumors per se tend to be more aggressive but are more responsive to chemotherapy. Whether +7q or +1q may be independent predictive markers for response to chemotherapy has to be clarified ultimately by multivariate analyses in larger studies with data on the cytogenetic constitution of tumors before and after preoperative chemotherapy. Isochromosomes of 7q have been identified as nonrandom aberrations in pediatric and adult Wilms' tumors (37–41) and it has been suggested that i(7q) is related to loss of a tumor suppressor gene at 7p (42, 43). Recently, the PTH-B1 (parathyroid hormone–responsive B1 gene) at 7p15 has been identified as a candidate gene for a Wilms' tumor-related suppressor gene (44). Future studies will have to clarify, whether the cytogenetic constitution may eventually serve as an additional variable to stratify patients in the management of Wilms' tumors.


   Acknowledgments
 
We thank C. Enders for excellent technical assistance.


   Footnotes
 
Grant support: North German Society of Urology.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: T. Schlomm and B. Gunawan contributed equally and should be considered as first authors.

Received 10/18/04; revised 3/11/05; accepted 3/21/05.


   References
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  1. Pritchard-Jones K. Controversies and advances in the management of Wilms' tumour. Arch Dis Child 2002;87:241–4.[Abstract/Free Full Text]
  2. Tournade MF, Com-Nougue C, Voute PA, et al. Results of the Sixth International Society of Pediatric Oncology Wilms' Tumor Trial and Study: a risk-adapted therapeutic approach in Wilms' tumor. J Clin Oncol 1993;11:1014–23.[Abstract/Free Full Text]
  3. Delemarre JF, Sandstedt B, Harms D, Boccon-Gibod L, Vujanic GM. The new SIOP (Stockholm) working classification of renal tumours of childhood. International Society of Paediatric Oncology. Med Pediatr Oncol 1996;26:145–6.[CrossRef][Medline]
  4. Godzinski J, Tournade MF, deKraker J, et al. Rarity of surgical complications after postchemotherapy nephrectomy for nephroblastoma. Experience of the International Society of Paediatric Oncology-Trial and Study "SIOP-9." International Society of Paediatric Oncology Nephroblastoma Trial and Study Committee. Eur J Pediatr Surg 1998;8:83–6.[Medline]
  5. Graf N, Tournade MF, de Kraker J. The role of preoperative chemotherapy in the management of Wilms' tumor. The SIOP studies. International Society of Pediatric Oncology. Urol Clin North Am 2000;27:443–54.[CrossRef][Medline]
  6. Tournade MF, Com-Nougue C, de Kraker J, et al. Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study. J Clin Oncol 2001;19:488–500.[Abstract/Free Full Text]
  7. Weirich A, Leuschner I, Harms D, et al. Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH. Ann Oncol 2001;12:311–9.[Abstract/Free Full Text]
  8. Marx M, Langer T, Graf N, et al. Multicentre analysis of anthracycline-induced cardiotoxicity in children following treatment according to the nephroblastoma studies SIOP No. 9/GPOH and SIOP 93–01/GPOH. Med Pediatr Oncol 2002;39:18–24.[CrossRef][Medline]
  9. Reinhard H, Semler O, Burger D, et al. Results of the SIOP 93–01/GPOH Trial and Study for the Treatment of Patients with Unilateral Nonmetastatic Wilms Tumor*. Klin Padiatr 2004;216:132–40.[CrossRef][Medline]
  10. Efferth T, Bode ME, Schulten HG, et al. Differential expression of the lung resistance-related protein/major vault protein in the histological compartments of nephroblastomas. Int J Oncol 2001a;19:163–8.[Medline]
  11. Efferth T, Schulten HG, Thelen P, et al. Differential expression of the heat shock protein 70 in the histological compartments of nephroblastomas. Anticancer Res 2001c;21:2915–20.[Medline]
  12. Efferth T, Thelen P, Schulten HG, et al. Differential expression of the multidrug resistance-related protein MRP1 in the histological compartments of nephroblastomas. Int J Oncol 2001b;19:367–71.[Medline]
  13. Granzen B, Efferth T, Keller U, et al. Differential expression of the drug resistance markers DNA topoisomerase II {alpha} and glutathione S-transferase-pi in the histological compartments of Wilms' tumors. Anticancer Res 2001;21:771–6.[Medline]
  14. Takahashi M, Yang XJ, Lavery TT, et al. Gene expression profiling of favorable histology Wilms tumors and its correlation with clinical features. Cancer Res 2002;62:6598–605.[Abstract/Free Full Text]
  15. Klamt B, Schulze M, Thate C, et al. Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlate with clinicopathological parameters. Genes Chromosomes Cancer 1998;22:287–94.[CrossRef][Medline]
  16. Hing S, Lu YJ, Summersgill B, et al. Gain of 1q is associated with adverse outcome in favorable histology Wilms' tumors. Am J Pathol 2001;158:393–8.[Abstract/Free Full Text]
  17. Bown N, Cotterill SJ, Roberts P, et al. Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the U.K. cancer cytogenetics group and the U.K. Children's Cancer Study Group. Med Pediatr Oncol 2002;38:11–21.[CrossRef][Medline]
  18. Peres EM, Savasan S, Cushing B, Abella S, Mohamed AN. Chromosome analyses of 16 cases of Wilms tumor: different pattern in unfavorable histology. Cancer Genet Cytogenet 2004;148:66–70.[CrossRef][Medline]
  19. Kalapurakal JA, Dome JS, Perlman EJ, et al. Management of Wilms' tumour: current practice and future goals. Lancet Oncol 2004;5:37–46.[CrossRef][Medline]
  20. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms tumors: results from the First National Wilms' Tumor Study. Cancer 1978;41:1937–48.[CrossRef][Medline]
  21. Gunawan B, Schulten HJ, von Heydebreck A, et al. Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours. J Pathol 2004;202:421–9.[CrossRef][Medline]
  22. Kallioniemi OP, Kallioniemi A, Piper J, et al. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer 1994;10:231–43.[Medline]
  23. Solinas-Toldo S, Wallrapp C, Muller-Pillasch F, et al. Mapping of chromosomal imbalances in pancreatic carcinoma by comparative genomic hybridization. Cancer Res 1996;56:3803–7.[Abstract/Free Full Text]
  24. Betts DR, Koesters R, Plüss HJ, Niggli F. Routine karyotyping in Wilms tumors. Cancer Genet Cytogenet 1997;96:151–6.[CrossRef][Medline]
  25. Hoglund M, Gisselsson D, Hansen GB, Mitelman F. Wilms tumors develop through two distinct karyotypic pathways. Cancer Genet Cytogenet 2004;150:9–15.[CrossRef][Medline]
  26. Kullendorff CM, Soller M, Wiebe T, Mertens F. Cytogenetic findings and clinical course in a consecutive series of Wilms tumors. Cancer Genet Cytogenet 2003;140:82–7.[CrossRef][Medline]
  27. Mertens F, Johansson B, Hoglund M, Mitelman F. Chromosomal imbalance maps of malignant solid tumors: a cytogenetic survey of 3185 neoplasms. Cancer Res 1997;57:2765–80.[Abstract/Free Full Text]
  28. Sheng WW, Soukup S, Bove K, Gotwals B, Lampkin B. Chromosome analysis of 31 Wilms' tumors. Cancer Res 1990;50:2786–93.
  29. Slater RM, Mannens MM. Cytogenetics and molecular genetics of Wilms' tumor of childhood. Cancer Genet Cytogenet 1992;61:111–21.[CrossRef][Medline]
  30. Solis V, Pritchard J, Cowell JK. Cytogenetic changes in Wilms' tumors. Cancer Genet Cytogenet 1988;34:223–34.[CrossRef][Medline]
  31. Soukup S, Gotwals B, Blough R, Lampkin B. Wilms tumor: summary of 54 cytogenetic analyses. Cancer Genet Cytogenet 1997;97:169–71.[CrossRef][Medline]
  32. Nakadate H, Tsuchiya T, Maseki N, et al. Correlation of chromosome abnormalities with presence or absence of WT1 deletions/mutations in Wilms tumor. Genes Chromosomes Cancer 1999;25:26–32.[CrossRef][Medline]
  33. Altura RA, Valentine M, Li H, et al. Identification of novel regions of deletion in familial Wilms' tumor by comparative genomic hybridization. Cancer Res 1996;56:3837–41.[Abstract/Free Full Text]
  34. Getman ME, Houseal TW, Miller GA, et al. Comparative genomic hybridization and its application to Wilms' tumorigenesis. Cytogenet Cell Genet 1998;82:284–90.[CrossRef][Medline]
  35. Steenman M, Redeker B, de Meulemeester M, et al. Comparative genomic hybridization analysis of Wilms tumors. Cytogenet Cell Genet 1997;77:296–303.[Medline]
  36. Kashiwagi H, Uchida K. Genome-wide profiling of gene amplification and deletion in cancer. Hum Cell 2000;13:135–41.[Medline]
  37. Fletcher JA, Renshaw AA. Isochromosome 7q in adult Wilms' tumor. Cancer Genet Cytogenet 1996;86:168–9.[CrossRef][Medline]
  38. Peier AM, Meloni AM, Erling MA, Sandberg AA. Involvement of chromosome 7 in Wilms tumor. Cancer Genet Cytogenet 1995;79:92–4.[CrossRef][Medline]
  39. Rubin BP, Pins MR, Nielsen GP, et al. Isochromosome 7q in adult Wilms' tumors: diagnostic and pathogenetic implications. Am J Surg Pathol 2000;24:1663–9.[CrossRef][Medline]
  40. Sandoval C, Stringel G, Ozkaynak MF, Tugal O, Jayabose S. Isochromosome 7q and Wilms tumor. Cancer Genet Cytogenet 1998;104:61–5.[CrossRef][Medline]
  41. Sreekantaiah C, Beneck D. Isochromosomes 7q and 17q in Wilms tumor. Cancer Genet Cytogenet 1998;106:84–6.[CrossRef][Medline]
  42. Grundy RG, Pritchard J, Scambler P, Cowell JK. Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour. Oncogene 1998;17:395–400.[CrossRef][Medline]
  43. Wilmore HP, White GF, Howell RT, Brown KW. Germline and somatic abnormalities of chromosome 7 in Wilms' tumor. Cancer Genet Cytogenet 1994;77:93–8.[CrossRef][Medline]
  44. Vernon EG, Malik K, Reynolds P, et al. The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms' tumour. Oncogene 2003;22:1371–80.[CrossRef][Medline]




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