Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens

Wallerand, Hervé; Bakkar, Ashraf; Medina, Sixtina Gil Diez de; Pairon, Jean‐Claude; Yang, Yuching; Vordos, Dimitri; Bittard, Hugues; Fauconnet, Sylvie; Kouyoumdjian, Jean‐Claude; Jaurand, Marie‐Claude; Zhang, Zuo‐Feng; Radvanyi, François; Thiery, Jean Paul; Chopin, Dominique

doi:10.1093/carcin/bgh275

Cited by 75 publications

(66 citation statements)

References 41 publications

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“…FGFR3 mutations were studied with the SNaPshot method (29). TP53 (exons 2-11), KRAS (exons 2-3), NRAS (exons 2-3), HRAS (exons 2-3) and PIK3CA (exons 2, 9, and 20) gene mutations were screened by direct sequencing with previously described primers and protocols (30,31), available on request. All mutations were confirmed by sequencing both strands of a second, independent PCR product.…”

Section: Data Production and Analysismentioning

confidence: 99%

A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis

et al. 2015

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Relationships between genetic alterations, such as co-occurrence or mutual exclusivity, are often observed in cancer, where their understanding may provide new insights into etiology and clinical management. In this study, we combined statistical analyses and computational modeling to explain patterns of genetic alterations seen in 178 patients with bladder tumors (either muscle-invasive or non-muscle-invasive). A statistical analysis on frequently altered genes identified pair associations, including co-occurrence or mutual exclusivity. Focusing on genetic alterations of protein-coding genes involved in growth factor receptor signaling, cell cycle, and apoptosis entry, we complemented this analysis with a literature search to focus on nine pairs of genetic alterations of our dataset, with subsequent verification in three other datasets available publicly. To understand the reasons and contexts of these patterns of associations while accounting for the dynamics of associated signaling pathways, we built a logical model. This model was validated first on published mutant mice data, then used to study patterns and to draw conclusions on counter-intuitive observations, allowing one to formulate predictions about conditions where combining genetic alterations benefits tumorigenesis. For example, while CDKN2A homozygous deletions occur in a context of FGFR3-activating mutations, our model suggests that additional PIK3CA mutation or p21CIP deletion would greatly favor invasiveness. Furthermore, the model sheds light on the temporal orders of gene alterations, for example, showing how mutual exclusivity of FGFR3 and TP53 mutations is interpretable if FGFR3 is mutated first. Overall, our work shows how to predict combinations of the major gene alterations leading to invasiveness through two main progression pathways in bladder cancer.

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Section: Data Production and Analysismentioning

confidence: 99%

A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis

et al. 2015

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“…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

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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

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“…Tobacco smoking has been established a major risk factor for bladder cancer because many carcinogens present in tobacco alter gene expression and damage DNA (Wallerand et al, 2005;Volanis et al, 2010). A metaanalysis summarizing the epidemiology of urinary tract cancer risk and cigarette smoking observed that current smokers have an approximately threefold higher risk than non-smokers (Zeegers et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation in PSCA is Associated with Bladder Cancer Susceptibility in a Korean Population

Lee¹,

Song²,

Kim³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. Materials and Methods: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. Results: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT =1.58, 95% CI= 1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. Conclusions: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.

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Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens

Cited by 75 publications

References 41 publications

A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis

A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis

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

Genetic Variation in PSCA is Associated with Bladder Cancer Susceptibility in a Korean Population

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