Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

Lindgren, David; Andersson, Anna; Chebil, Gunilla; Guðjónsson, Sigurður; Borg, Åke; Månsson, Wiking; Fioretos, Thoas; Höglund, Mattias

doi:10.1038/sj.onc.1209249

Cited by 121 publications

(105 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of the 63 reports selected for detailed evaluation, 33 were excluded as duplications or because they lacked key data. The final meta-analysis was carried out on the remaining 30 studies (Billerey et al, 2001;Kimura et al, 2001;Bakkar et al, 2003;Rieger-Christ et al, 2003;van Rhijn et al, 2003van Rhijn et al, , 2004Hernández et al, 2005;Jebar et al, 2005;van der Aa et al, 2005;Wallerand et al, 2005;Hernández et al, 2006;Lindgren et al, 2006;Tomlinson et al, 2007;van Oers et al, 2007;Burger et al, 2008;Junker et al, 2008;Eltze et al, 2009;Ouerhani et al, 2009;van Oers et al, 2009;Zieger et al, 2009;Bakkar et al, 2010;Bodoor et al, 2010;Kompier et al, 2010;Miyake et al, 2010;van Rhijn et al, 2010;Al-Ahmadie et al, 2011;Dodurga et al, 2011;Serizawa et al, 2011;Sjödahl et al, 2011;van Rhijn et al, 2012). Twenty-five of the studies (Table 1A) investigated the association between FGFR3 mutations and grade or stage, while the other 13 studies (Table 1B) investigated the prognostic value of FGFR3 mutations for BC.…”

Section: Resultsmentioning

confidence: 99%

Clinical significance of fibroblast growth factor receptor-3 mutations in bladder cancer: a systematic review and meta-analysis

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene are frequently found in bladder cancer, but their prognostic value remains controversial. To globally summarize the association between FGFR3 mutations and the grade and stage of bladder cancer, and to analyze the predictive role of FGFR3 mutations with respect to survival, eligible studies were identified and assessed for quality through multiple search strategies. Risk ratio (RR) data were collected from studies comparing the number of FGFR3 mutants among low-grade and early-stage bladder cancer patients to the number among high-grade and late-stage patients. Hazard ratio (HR) data were collected from studies comparing survival in patients with mutant FGFR3 genes to those with wild-type genes. Studies were pooled, and the RRs of grade and stage and the HRs of survival were

show abstract

Section: Resultsmentioning

confidence: 99%

Clinical significance of fibroblast growth factor receptor-3 mutations in bladder cancer: a systematic review and meta-analysis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…FGFR3 and TP53 mutations have not been identified in normal bladder epithelium from patients with confirmed urothelial carcinoma, suggesting the mutations were somatic. 15,23 Additional molecular studies by Jebar et al, 9 have found that FGFR3 mutations are mutually exclusive of Ras gene mutations in urothelial cell carcinoma (Table 2).…”

Section: Discussionmentioning

confidence: 99%

FGFR3 and TP53 mutation analysis in inverted urothelial papilloma: incidence and etiological considerations

et al. 2009

View full text Add to dashboard Cite

Urothelial papillomas and low-grade urothelial carcinomas have shown a high incidence of fibroblast growth factor receptor 3 (FGFR3) mutations and are associated with a favorable prognosis. The association of FGFR3 mutations with inverted papillomas is less known. We analyzed 20 cases of inverted papilloma in the urinary tract. Mutations of FGFR3 (exons 7, 10, and 15) and TP53 genes were evaluated by DNA sequencing in these cases. Point mutations of the FGFR3 gene were identified in 45% (9 of 20) of inverted papillomas with four cases exhibiting mutations at multiple exons. Seven cases had exon 7 mutations containing R248C, S249T, L259L, P260P, and V266M. Two cases had exon 10 and 15 mutations including A366D, H412H, E627D, D641N, and H643D; five cases had N653H. The most frequent mutation was identified at R248C. None of the inverted papillomas exhibited mutations in TP53. During a mean follow-up of 78 months, none had recurrence or developed urothelial carcinoma. These findings support the concept that low-grade and low-stage urothelial neoplasms arise in a background of molecular changes that are distinctly different from the molecular changes of high-grade and high-stage urothelial cancers. Modern Pathology ( Keywords: urinary bladder; urinary tract; inverted papilloma; fibroblast growth factor receptor 3; tumorigenesis; TP mutationsThe fibroblast growth factor receptor 3 (FGFR3) is a member of a family of tyrosine kinase receptors and is composed of an extracellular ligand-binding domain, a transmembrane region, and a cytoplasmic domain with tyrosine kinase activity. Ligand binding causes receptor dimerization and subsequent activation of intracellular tyrosines. Activating mutations of FGFR3 gene lead to constitutive activation of the receptor subsequently inducing the downstream molecular pathogenesis. Activating point mutations of FGFR3 have been associated with autosomal dominant dwarfism and severe achondroplasia. An oncogenic role for FGFR3 in human cancer has emerged recently and FGFR3 mutations were reported to be associated with multiple myeloma, urothelial, and cervical cancers.Urothelial carcinomas harboring FGRFR3 mutations, in general, tend to be of low histological grade and of low pathological stage, and consequently are associated with a more favorable clinical outcome.

show abstract

“…Cells were grown in 1:1 DMEM:F12 medium (Gibco Life Sciences, Carlsbad, CA) supplemented with 10% serum and antibiotics. Tissue sections from transurethrally resected primary tumors were obtained from a consecutive series of UC patients (14). Of these, the 57 patients presenting from 2001 to 2004 and for whom tissue sections were available at the Department of Pathology, Lund University Hospital, were selected.…”

Section: Methodsmentioning

confidence: 99%

Distinct Mitotic Segregation Errors Mediate Chromosomal Instability in Aggressive Urothelial Cancers

Jin¹,

Stewénius²,

Lindgren³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Chromosomal instability (CIN) is believed to have an important role in the pathogenesis of urothelial cancer (UC).The aim of this study was to evaluate whether disturbances of mitotic segregation contribute to CIN in UC, if these processes have any effect on the course of disease, and how deregulation of these mechanisms affects tumor cell growth. Experimental Design: We developed molecular cytogenetic methods to classify mitotic segregation abnormalities in a panel of UC cell lines. Mitotic instabilities were then scored in biopsies from 52 UC patients and compared with the outcome of tumor disease. Finally, UC cells were exposed in vitro to a telomerase inhibitor to assess how this affects mitotic stability and cell proliferation. Results:Three distinct chromosome segregation abnormalities were identified: (a) telomere dysfunction, which triggers structural rearrangements and loss of chromosomes through anaphase bridging; (b) sister chromatid nondisjunction, which generates discrete chromosomal copy number variations; and (c) supernumerary centrosomes, which cause dramatic shifts in chromosome copy number through multipolar cell division. Chromosome segregation errors were already present in preinvasive tumors and a high rate mitotic instability was an independent predictor of poor survival. However, induction of even higher levels of the same segregation abnormalities in UC cells by telomerase inhibition in vitro led to reduced tumor cell proliferation and clonogenic survival. Conclusion: Several distinct chromosome segregation errors contribute to CIN in UC, and the rate of such mitotic errors has a significant effect on the clinical course. Efficient tumor cell proliferation may depend on the tight endogenous control of these processes.

show abstract

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

Cited by 121 publications

References 39 publications

Clinical significance of fibroblast growth factor receptor-3 mutations in bladder cancer: a systematic review and meta-analysis

Clinical significance of fibroblast growth factor receptor-3 mutations in bladder cancer: a systematic review and meta-analysis

FGFR3 and TP53 mutation analysis in inverted urothelial papilloma: incidence and etiological considerations

Distinct Mitotic Segregation Errors Mediate Chromosomal Instability in Aggressive Urothelial Cancers

Contact Info

Product

Resources

About