Pouessel, D, Neuzillet, Y, Mertens, LS et al. (35 more authors) (2016) Tumor Heterogeneity of Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations in Invasive Bladder Cancer: Implications for Peri-Operative anti-FGFR3 Treatment. Annals of Oncology, 27 (7). pp. 1311-1316. ISSN 0923-7534
Abstract
Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Authors, 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Annals of Oncology following peer review. The version of record Pouessel, D, Neuzillet, Y, Mertens, LS, van der Heijden, MS, de Jong, J, Sanders, J, Peters, D, Leroy, K, Manceau, A, Maille, P, Soyeux, P, Moktefi, A, Semprez, F, Vordos, D, de la Taille, A, Hurst, CD, Tomlinson, DC, Harnden, P, Bostrom, PJ, Mirtti, T, Hoernblas, S, Loriot, Y, Houede, N, Chevreau, C, Beuzeboc, P, Shariat, SF, Sagalowsky, AI, Ashfaq, R, Burger, M, Jewett, MAS, Zlotta, AR, Broeks, A, Bapat, B, Knowles, MA, Lotan, Y, van der Kwast, TH, Culine, S and van Rhijn, BWG (2016) Tumor Heterogeneity of Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations in Invasive Bladder Cancer: Implications for Peri-Operative anti-FGFR3 Treatment. Annals of Oncology. ISSN 0923-7534 is available online at: http://dx.doi.org/10.1093/annonc/mdw170 |
Keywords: | FGFR3; mutations; heterogeneity; bladder; cancer; targeted therapy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Oncology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Section of Experimental Oncology (Leeds) |
Funding Information: | Funder Grant number Cancer Research UK C6228/A12512 |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Apr 2016 11:37 |
Last Modified: | 19 Apr 2017 00:54 |
Published Version: | http://dx.doi.org/10.1093/annonc/mdw170 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/annonc/mdw170 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98964 |