title: Utility of ATP7B in prediction of response to platinum-based chemotherapy in urothelial bladder cancer.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Although resistance is complex, LOH at the ATP7B locus might be useful in predicting chemotherapy response and needs further evaluation.
authors.affiliation: Urologische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. sebastian.schmid@lrz.tum.de; http://www.mri.tum.de/urologie.
authors.forename: Sebastian Christoph
authors.initials: SC
authors.lastname: Schmid
authors.forename: Tibor
authors.initials: T
authors.lastname: Schuster
authors.forename: Thomas
authors.initials: T
authors.lastname: Horn
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gschwend
authors.forename: Uwe
authors.initials: U
authors.lastname: Treiber
authors.forename: Gregor
authors.initials: G
authors.lastname: Weirich
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002882:Chromosomes, Human, Pair 13; D002945:Cisplatin / Q000627:therapeutic use*; D000073840:Copper-Transporting ATPases; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D017931:DNA Primers; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin
keywords: ATP7B; LOH; bladder cancer; chemotherapy; cisplatin; urothelial carcinoma