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

Liu, X.; Zhang, W.; Geng, Dechun; He, Jing; Zhao, Yulan; Liu, Yu

doi:10.4238/2014.february.20.12

Cited by 38 publications

(19 citation statements)

References 43 publications

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“…Analyzing the potential effect of FGFR3 driver mutations on survival of lung cancer patients, we observed a trend toward better survival for FGFR3 mutations in lung adenocarcinoma, compared with lung adenocarcinoma patients with wild-type FGFR3 and those harboring KRAS mutation, similar to as reported in the bladder and skin cancer [33]. Thus, FGFR3 mutation represents an opportunity for targeted therapy in lung adenocarcinoma.…”

Section: Discussionsupporting

confidence: 77%

Drug-sensitiveFGFR3 mutations in lung adenocarcinoma

et al. 2017

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BackgroundLung cancer is the leading cause of cancer-related deaths across the world. In this study, we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin.Materials and methodsForty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500 × (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry. NIH/3T3 cells over expressing mutant and wild-type FGFR3 constructs were characterized for anchorage independent growth, constitutive activation, tumor formation and sensitivity to FGFR inhibitors using in vitro and xenograft mouse models.ResultsWe present the first spectrum of actionable alterations in lung adenocarcinoma tumors of Indian origin, and shows that mutations of FGFR3 are present in 20 of 363 (5.5%) patients. These FGFR3 mutations are constitutively active and oncogenic when ectopically expressed in NIH/3T3 cells and using a xenograft model in NOD/SCID mice. Inhibition of FGFR3 kinase activity inhibits transformation of NIH/3T3 overexpressing FGFR3 constructs and growth of tumors driven by FGFR3 in the xenograft models. The reduction in tumor size in the mouse is paralleled by a reduction in the amounts of phospho-ERK, validating the in vitro findings. Interestingly, the FGFR3 mutations are significantly higher in a proportion of younger patients and show a trend toward better overall survival, compared with patients lacking actionable alterations or those harboring KRAS mutations.ConclusionWe present the first actionable mutation spectrum in Indian lung cancer genome. These findings implicate FGFR3 as a novel therapeutic in lung adenocarcinoma.

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Section: Discussionsupporting

confidence: 77%

Drug-sensitiveFGFR3 mutations in lung adenocarcinoma

et al. 2017

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“…FGFR3 mutations have been associated with low-grade bladder tumors and a favorable prognosis and survival rate, whereas overexpression of the FGFR3 wildtype protein has been correlated with higher stage tumors (Iyer and Milowsky, 2013;Liu et al, 2014). Recently, it was found that high BGN expression in bladder cancer was associated with reduced tumor growth and a favorable prognosis (Niedworok et al, 2013).…”

Section: Discussionmentioning

confidence: 98%

Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis

Winge

Nielsen

Jørgensen

et al. 2015

Molecular and Cellular Endocrinology

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“…FGFR genes are deregulated in solid tumors by amplification, translocation or mutation [16]. FGFR3 mutations are particulary frequent in bladder cancer, where they are associated with low grade, early stage, and better survival [17]. We observed a FGFR3 missense mutation in two thymic carcinomas.…”

Section: Discussionmentioning

confidence: 88%

Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets

Enkner

Pichlhöfer

Zaharie

et al. 2016

Pathol. Oncol. Res.

108

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Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16INK4A, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s12253-016-0144-8) contains supplementary material, which is available to authorized users.

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

Cited by 38 publications

References 43 publications

Drug-sensitiveFGFR3 mutations in lung adenocarcinoma

Drug-sensitiveFGFR3 mutations in lung adenocarcinoma

Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis

Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets

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