Telomeric fusions in a Wilms' tumor

Fett‐Conte, Agnes Cristina; Liedtke, Humberto; Chaves, Helder; Thomé, Jorge Alberto; Tajara, Eloíza H.

doi:10.1016/0165-4608(93)90092-z

Cited by 13 publications

(5 citation statements)

References 14 publications

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“…In WT cells, telomeres are typically shorter than in somatic cells from the same patients (21). Furthermore, telomeric fusions (22) and chromosomal aberrations derived from breakage-fusion-bridge cycles have been described (23). However, the prevalence of telomere-dependent CIN in WT is not known, and it has not been studied whether it has any implications for clonal evolution and the course of disease.…”

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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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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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“…In this scenario, as telomeres shorten with each cell cycle the “sticky” ends of chromosomes become prone to fusions [100] leading to subsequent chromosomal instability [100,101,102,103] and offering a mechanism for a continuous rearrangement of chromosome structure that might contribute to oncogene amplification and tumor suppressor gene deletion [104,105]. In fact, concurrent telomere shortening and genomic instability have been observed in the majority of embryonic tumors including: Wilms’ tumor [106,107], MB [108,109], NB [110,111] and rhabdomyosarcoma [112,113]. The view represented by the stem cell origin of embryonal tumors implies that the genetic alterations which lead to cancer accumulate in embryonal stem cells rather than mature cells.…”

Section: G-quadruplexes As a Potential Cancer Therapeutic Targetsmentioning

confidence: 99%

“…Down-regulation of telomerase activity has been shown to induce cancer cell growth arrest and differentiation, which might predict a close correlation between telomerase activity levels and clinical outcome, while tumors with sustained telomerase activity might therefore become choice targets for telomerase directed therapy [116,117,118,119]. Telomere maintenance biology have been studied in the majority of embryonic tumors including Wilms’ tumor [106,107,120], Ewing’s sarcoma [121,122,123], hepatoblastoma [8,124], MB [108,109,125,126], NB [127,128] and rhabdomyosarcoma [112,129]. We will focus below on pediatric malignancies of the central and peripheral nervous system MB and NB.…”

Section: G-quadruplexes As a Potential Cancer Therapeutic Targetsmentioning

confidence: 99%

G-Quadruplexes as Potential Therapeutic Targets for Embryonal Tumors

et al. 2013

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Embryonal tumors include a heterogeneous group of highly malignant neoplasms that primarily affect infants and children and are characterized by a high rate of mortality and treatment-related morbidity, hence improved therapies are clearly needed. G-quadruplexes are special secondary structures adopted in guanine (G)-rich DNA sequences that are often present in biologically important regions, e.g. at the end of telomeres and in the regulatory regions of oncogenes such as MYC. Owing to the significant roles that both telomeres and MYC play in cancer cell biology, G-quadruplexes have been viewed as emerging therapeutic targets in oncology and as tools for novel anticancer drug design. Several compounds that target these structures have shown promising anticancer activity in tumor xenograft models and some of them have entered Phase II clinical trials. In this review we examine approaches to DNA targeted cancer therapy, summarize the recent developments of G-quadruplex ligands as anticancer drugs and speculate on the future direction of such structures as a potential novel therapeutic strategy for embryonal tumors of the nervous system.

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“…Cytogenetic studies of certain tumors such as giant cell tumor of bone (GCT) have tas demonstrated repeatedly in about 75% of CCT patients [1][2][3]. In addition, telomeric fusions have been reported in Wilms' tumor cells [4].…”

Section: Introductionmentioning

confidence: 99%