title: No significant role for beta tubulin mutations and mismatch repair defects in ovarian cancer resistance to paclitaxel/cisplatin.
abstract: BACKGROUND
  The mechanisms of chemoresistance in ovarian cancer patients remain largely to be elucidated. Paclitaxel/cisplatin combination is the standard chemotherapeutic treatment for this disease, although some patients do not respond to therapy. Our goals were to investigate whether TUBB mutations and mismatch repair defects underlie paclitaxel and cisplatin resistance.
  
  
  METHODS
  Thirty-four patients with primary ovarian carcinomas (26 serous and eight clear cell carcinomas) treated with paclitaxel/cisplatin were analysed. TUBB exon 4 was analysed by nested PCR after a first round PCR using intronic primers. Microsatellite analysis was performed with the quasimonomorphic markers BAT 26 and BAT 34.
  
  
  RESULTS
  Twenty-two of the 34 ovarian cancers (64.7%) presented residual tumour after surgery, seven of which (7/22; 31.8%) were shown to be chemoresistant (five serous and two clear cell tumours). Sequence analysis did not find any mutation in TUBB exon 4. Microsatellite instability was not detected in any of the ovarian carcinomas.
  
  
  CONCLUSIONS
  We conclude that TUBB exon 4 mutations and mismatch repair defects do not play a significant role in paclitaxel/cisplatin resistance.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, 4200-072 Porto, Portugal. barbara-mesquita@portugalmail.pt
authors.forename: Bárbara
authors.initials: B
authors.lastname: Mesquita
authors.forename: Isabel
authors.initials: I
authors.lastname: Veiga
authors.forename: Deolinda
authors.initials: D
authors.lastname: Pereira
authors.forename: Ana
authors.initials: A
authors.lastname: Tavares
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Pinto
authors.forename: Carla
authors.initials: C
authors.lastname: Pinto
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: Sérgio
authors.initials: S
authors.lastname: Castedo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D020137:Base Pair Mismatch; D002945:Cisplatin / Q000627:therapeutic use*; D004260:DNA Repair; D004261:DNA Replication; D019008:Drug Resistance, Neoplasm; D005091:Exons; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014404:Tubulin / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel; D002945:Cisplatin