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†

Bown, Nick; Cotterill, SJ; Roberts, Paul; Griffiths, Mike; Larkins, S.; Hibbert, Steve; Middleton, Helen; Kelsey, Anna; Tritton, Denise; Mitchell, Chris

doi:10.1002/mpo.1258

Cited by 77 publications

(57 citation statements)

References 22 publications

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“…Eleven primary WT (cases [1][2][3][4][5][6][7][8][9][10][11] and one established WT cell line (case 12) were characterized by G banding, combined binary and ratio labeling, and subtelomeric FISH (Table 1). Of the primary tumors, eight exhibited intermediate-risk histology and three had high-risk histology: cases 2 and 7 were of blastemal predominant histology and case 11 was diffusely anaplastic.…”

Section: Resultsmentioning

confidence: 99%

Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors

Stewénius¹,

Jin²,

Øra

et al. 2007

Clinical Cancer Research

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Purpose: In many childhood neoplasms, prognostic subgroups have been defined based on specific chromosome changes. In Wilms' tumor (WT), such subclassification has been hampered by the diverse and relatively unspecific pattern of chromosomal imbalances present in these tumors. Unspecific patterns of cytogenetic imbalances in tumors are often caused by mitotic segregation errors due to short dysfunctional telomeres. As an alternative to cytogenetic classification, we therefore have evaluated whether the rate of telomere-dependent chromosomal instability could influence the clinical course in WT patients. Experimental Design: Telomere function and mitotic segregation errors were assessed in 12 cultured tumors and in tumor tissue sections from 41WT patients. Results: Abnormal telomere shortening was found in cultured cells and in tissue sections from highly aggressive tumors. In vitro, dysfunctional telomeres were associated to specific cell division abnormalities, including anaphase bridges and multipolar mitoses. Assessment of mitotic figures in tissue sections revealed that anaphase bridges and multipolar mitoses were predominantly, but not exclusively, present in high-risk tumors and were predictors of poor event-free and overall survival. Conclusions: Telomere-dependent mitotic instability is present in a subgroup of WT, predominately consisting of high-risk tumors.

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Section: Resultsmentioning

confidence: 99%

Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors

Stewénius¹,

Jin²,

Øra

et al. 2007

Clinical Cancer Research

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“…59 Retrospective studies conducted in the United Kingdom demonstrated an association between 1q gain and tumor recurrence. [60][61][62][63] Interestingly, an association between 1q gain and loss of chromosomes 1p and 16q was noted, indicating that the prognostic significance of LOH at 1p and 16q may not be independent of 1q gain.…”

Section: Chromosome 1q Gainmentioning

confidence: 99%

Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration

Dome

Graf

Geller

et al. 2015

JCO

316

313

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Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level.

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“…Using comparative genomic hybridization and microarrays, the critical region of 17q amplification has been defined around 17q12-q21 (8). Amplification at 17q is associated with several malignancies, such as breast, gastric, pancreatic, and neuroblastomas (9)(10)(11)(12)(13)(14)(15). The 17q12-q21 region is a gene-rich area that contains several candidate cancer genes, including PPP1R1B/DARPP-32, ERBB2, TOP2A, and GRB7.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dissection of 17q12 Amplicon in Upper Gastrointestinal Adenocarcinomas

Maqani

Belkhiri

Moskaluk

et al. 2006

Molecular Cancer Research

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DNA amplification at 17q is frequently detected in upper gastrointestinal adenocarcinomas (UGC; stomach and esophagus). In this study, we did fluorescence in situ hybridization on a tissue microarray that contained 304 UGCs and 89 normal stomach samples using a f168-kb BAC clone (CTD-2019C10) that maps to 17q12-q21.1. This 168-kb region contains the following genes: PPP1R1B/DARPP-32, STARD3, TCAP, PNMT, PERLD1, ERBB2, C17orf37, and GRB7 as well as the first two exons of ZNFN1A3. DNA amplification (z5 signals) was detected in 85 of 282 (30%) of UGCs, and high-level amplification (z10 signals) was seen in 28 of 282 (10%) of all tumors. Adenocarcinomas of gastroesophageal junction and lower esophagus had the highest frequency of amplification (45%) compared with stomach tumors (27%; P = 0.04). On the other hand, 38% of tumors with intestinal-type morphology had amplification compared with 26% of diffuse-type tumors (P = 0.02). We further did quantitative real-time reverse transcription-PCR on 74 frozen tissue samples from UGCs for 11 genes located within or adjacent to the boundaries of this f168-kb genomic region. These genes include all 9 genes that are fully or partially located inside the CTD-2019C10 clone as well as 2 additional adjacent genes (NEUROD and TOP2A). Overexpression of PPP1R1B/DARPP-32, TCAP, and TOP2A was seen in approximately half of the tumors, whereas STARD3 and ZNFN1A3 were rarely overexpressed (12%). Interestingly, there was a statistical correlation between expression of all 8 genes that map between PPP1R1B/DARPP-32 and GRB7, whereas expression of NEUROD, ZNFN1A3, and TOP2A that are partially inside or adjacent to the boundaries of the CTD-2019C10 clone did not correlate with the expression of any of these 8 genes. These data show a transcriptionally active oncogenomic region bounded by PPP1R1B/DARPP-32 and GRB7 in UGCs and provide further insight into expression levels of several critical genes. (Mol Cancer Res 2006;4(7):449 -55)

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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†

Abstract: Loss of chromosome 22 identifies high risk Wilms tumors. The prognostic significance of 1q gain, 16q loss and unbalanced translocation der(16)t(1q;16q) is unresolved and warrants further investigation.

Cited by 77 publications

References 22 publications

Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors

Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors

Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration

Molecular Dissection of 17q12 Amplicon in Upper Gastrointestinal Adenocarcinomas

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