BACKGROUND: Platinum-based chemotherapy is the treatment of choice for metastatic urothelial carcinoma, which is limited by primary and secondary resistance of the tumour. The Cu(2+) transporting beta polypeptide ATPase (ATP7B) is believed to play a role in this resistance. The aim of this study was to screen the ATP7B gene for mutations and loss of heterozygosity in bladder cancer and to evaluate their impact on chemotherapy resistance. MATERIALS AND METHODS: DNA extracted from 17 patients with metastatic bladder cancer was analyzed by DNA sequencing, and microsatellite analysis. RESULTS: We found 12 non-synonymous mutations and 20 synonymous mutations out of which 11 and 15, respectively, have not been previously described. Results were correlated with response to platinum-based chemotherapy: 65% of patients exhibited LOH of the ATP7B locus on chromosome 13q14.3, with a tendency to have a better response to chemotherapy. CONCLUSION: Although resistance is complex, LOH at the ATP7B locus might be useful in predicting chemotherapy response and needs further evaluation.
BACKGROUND:Platinum-based chemotherapy is the treatment of choice for metastatic urothelial carcinoma, which is limited by primary and secondary resistance of the tumour. The Cu(2+) transporting beta polypeptide ATPase (ATP7B) is believed to play a role in this resistance. The aim of this study was to screen the ATP7B gene for mutations and loss of heterozygosity in bladder cancer and to evaluate their impact on chemotherapy resistance. MATERIALS AND METHODS: DNA extracted from 17 patients with metastatic bladder cancer was analyzed by DNA sequencing, and microsatellite analysis. RESULTS: We found 12 non-synonymous mutations and 20 synonymous mutations out of which 11 and 15, respectively, have not been previously described. Results were correlated with response to platinum-based chemotherapy: 65% of patients exhibited LOH of the ATP7B locus on chromosome 13q14.3, with a tendency to have a better response to chemotherapy. CONCLUSION: Although resistance is complex, LOH at the ATP7B locus might be useful in predicting chemotherapy response and needs further evaluation.
Authors: Sebastian C Schmid; Leonore Thümer; Tibor Schuster; Thomas Horn; Florian Kurtz; Julia Slotta-Huspenina; Judith Seebach; Michael Straub; Tobias Maurer; Michael Autenrieth; Hubert Kübler; Margitta Retz; Ulrike Protzer; Jürgen E Gschwend; Dieter Hoffmann Journal: Infect Agent Cancer Date: 2015-09-21 Impact factor: 2.965
Authors: Margaretha A Skowron; Patrick Petzsch; Karin Hardt; Nicholas Wagner; Manfred Beier; Stefanie Stepanow; Matthias Drechsler; Harald Rieder; Karl Köhrer; Günter Niegisch; Michèle J Hoffmann; Wolfgang A Schulz Journal: Sci Rep Date: 2019-10-09 Impact factor: 4.379
Authors: Elizabeth A Guancial; Deepak Kilari; Guang-Qian Xiao; Sohaib H Abu-Farsakh; Andrea Baran; Edward M Messing; Eric S Kim Journal: PLoS One Date: 2016-05-17 Impact factor: 3.240