Utility of ATP7B in prediction of response to platinum-based chemotherapy in urothelial bladder cancer

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 t...

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Bibliographic Details
Published in:Anticancer research 2013-09, Vol.33 (9), p.3731-3737
Main Authors: Schmid, Sebastian Christoph, Schuster, Tibor, Horn, Thomas, Gschwend, Jürgen, Treiber, Uwe, Weirich, Gregor
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Adult
Aged
Antineoplastic Agents - therapeutic use
Base Sequence
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Chromosomes, Human, Pair 13
Cisplatin - therapeutic use
Copper-transporting ATPases
DNA Primers
Drug Resistance, Neoplasm - genetics
Humans
Loss of Heterozygosity
Microsatellite Repeats - genetics
Middle Aged
Mutation
Polymorphism, Genetic
Prognosis
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - enzymology
Urinary Bladder Neoplasms - genetics
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Summary: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. DNA extracted from 17 patients with metastatic bladder cancer was analyzed by DNA sequencing, and microsatellite analysis. 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. Although resistance is complex, LOH at the ATP7B locus might be useful in predicting chemotherapy response and needs further evaluation.
ISSN:1791-7530