Recent Advances in the Genetics of Childhood Renal Cancers: A report of the 3rd International Conference on the molecular and clinical genetics of childhood renal tumors, together with the Mitchell Ross Symposium on anaplastic and other high risk embryonal tumors of childhood, 8-10th April 1999, Wistar Institute, Philadelphia, PA

Jones, Kathryn; Grundy, Paul E.; Coppes, Max J.

doi:10.1002/1096-911x(200008)35:2<126::aid-mpo8>3.0.co;2-4

Cited by 8 publications

(5 citation statements)

References 9 publications

(8 reference statements)

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“…However, 15% to 20% of WT patients experience relapse associated with resistance to treatments and poor prognosis (3,4). An increased probability of relapse and mortality correlates with anaplasia and metastasis (5,6) as well as increased chromosomal anomalies (7,8).…”

Section: Introductionmentioning

confidence: 99%

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

Nguyen

Béland²,

Gaitan³

et al. 2009

Molecular Cancer Research

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Current therapeutic strategies against Wilms' tumor (WT) reach 80% to 85% success rate. In spite of this, a remaining 15% to 20% of tumors relapse and are associated with increased metastasis and poor prognosis. To identify new regulators of WT progression, we screened for developmental target genes of Pax2, a key regulator of kidney development and a WT signature gene. We show that one of these target genes, calcineurin A-binding protein (CnABP), is coexpressed with Pax2 during kidney development and is overexpressed in >70% of WT samples analyzed. The CnABP gene encodes a novel protein product conserved in higher vertebrates. We show that CnABP promotes cell proliferation and migration in cell culture experiments. Biochemical analyses additionally identified an interaction between CnABP and calcineurin Aβ, the catalytic subunit of the calcium-responsive serine/ threonine phosphatase calcineurin. We show that this interaction leads to the inhibition of calcineurin phosphatase activity and prevents nuclear factor of activated T-cell (NFAT) nuclear translocation. Inhibition of NFAT nuclear localization results in decreased NFAT transcriptional response. Together, these data identify a new modulator of calcineurin signaling up-regulated in WTs. (Mol Cancer Res 2009;7(6):821-31)

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Section: Introductionmentioning

confidence: 99%

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

Nguyen

Béland²,

Gaitan³

et al. 2009

Molecular Cancer Research

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“…Whereas 80% to 85% of Wilms tumor patients survive the disease, there remain 15% to 20% that experience relapse and low survival rates despite aggressive retreatment (2). On the other hand, those patients cured of their disease frequently experience adverse side effects from therapy (3).…”

Section: Introductionmentioning

confidence: 99%

A Gene Expression Signature for Relapse of Primary Wilms Tumors

Kessler

Yeger

et al. 2005

Cancer Research

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Anaplastic histology and metastasis are each associated with higher relapse and mortality rates in Wilms tumor patients. However, not all anaplastic tumors relapse and some nonanaplastic tumors relapse unexpectedly. To identify more accurate early prognostic indicators, we analyzed expression of 4,900 cancer-related genes in 26 primary Wilms tumors. This analysis revealed that expression of a set of four genes predicts future relapse of primary Wilms tumors with high accuracy, independent of anaplasia. Random permutation testing of this prognostic gene expression signature yielded P = = = 0.003. Real-time reverse transcription-PCR analysis of the four genes in an independent primary tumor set resulted in correct prediction of future relapse with an accuracy of 92%. One of the four genes in the prognostic signature, CCAAT/ /enhancer binding protein h h (C/ /EBPB), is expressed at higher levels in both primary relapsing tumors and metastatic tumors than in primary nonrelapsing tumors. Short interfering RNA-mediated down-regulation of C/ / /EBPB expression in WiT49, a cell line derived from a metastatic Wilms tumor, resulted in spontaneous apoptosis. These findings suggest that C/ / /EBPB is a critical survival factor for Wilms tumor cells and that its expression contributes to the prognosis of Wilms tumor patients. (Cancer Res 2005; 65(7): 2592-601)

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“…However, biphasic and monophasic tumors are also encountered 3. Although 80–85% of WT patients survive the disease,6 blastemal and anaplastic WT experience relapse and are associated with poor prognosis 7. However, not all anaplastic tumors relapse and occasionally cases with favorable histology can relapse unexpectedly 7.…”

mentioning

confidence: 99%

Identification of limited regions of genetic aberrations in patients affected with Wilms' tumor using a tiling‐path chromosome 22 array

Benetkiewicz

Ståhl

Gördör

et al. 2006

Intl Journal of Cancer

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Wilms' tumor (WT) is one of the most common solid tumors of childhood. The genetics of this disorder is complex and few studies have suggested allelic loss of chromosome 22 as a frequent aberration. To assess tumor‐ and possible germline‐specific regions affected with gene copy number variations on this chromosome, we applied a high‐resolution genomic clone‐based chromosome 22 array to a series of 28 WT samples and the paired blood‐derived DNA of the patients. The group of tumors was enriched for cases with metastases, relapse or fatal outcome, criteria that were expected to yield a higher number of alterations on chromosome 22. Overall, the array‐based form of comparative genomic hybridization (array‐CGH) analysis revealed genomic changes in 53% (15 out of 28) of cases. We identified hemizygous deletion of the whole arm of 22q in 3 tumors (11%). Furthermore, a complex amplifier genotype was detected in 8 samples, presenting regions of gain along the chromosome, which defined 7 distinct minimal overlapping segments. The distribution of aberrations in 4 additional cases displaying regional genomic imbalances delimited 2 tumor suppressor/oncogene candidate loci, 1 in the proximal and the other in the terminal part of 22q. Analysis of these regions revealed the presence of several candidate genes that may play a role in the development of WT. These findings demonstrate the power of array‐CGH in the determination of DNA copy number alterations and further strength the notion that WT‐associated genes exist on this chromosome. © 2006 Wiley‐Liss, Inc.

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Cited by 8 publications

References 9 publications

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

A Gene Expression Signature for Relapse of Primary Wilms Tumors

Identification of limited regions of genetic aberrations in patients affected with Wilms' tumor using a tiling‐path chromosome 22 array

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