No significant role for beta tubulin mutations and mismatch repair defects in ovarian cancer resistance to paclitaxel/cisplatin.
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.
Mesquita
Bárbara
B
Department of Genetics, Portuguese Oncology Institute, 4200-072 Porto, Portugal. barbara-mesquita@portugalmail.pt
Veiga
Isabel
I
Pereira
Deolinda
D
Tavares
Ana
A
Pinto
Isabel M
IM
Pinto
Carla
C
Teixeira
Manuel R
MR
Castedo
Sérgio
S
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*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel; D002945:Cisplatin