Background: The interaction between paclitaxel and its target, beta tubulin, is essential for effective cytotoxicity. Alterations or mutation of beta tubulin have the potential to alter paclitaxel binding and confer a drug resistant phenotype.
Materials and methods: Twenty-nine paired tumor samples from women with ovarian cancer were examined to evaluate the incidence of exon four mutations in tumors with evolving paclitaxel resistance. Tissue was dissected from five-micron paraffin slices and analyzed for mutations in exon four of human beta tubulin by PCR-SSCP. Nested PCR primers generated three partially overlapping or neighboring fragments corresponding to exon four of beta tubulin. 32P labeled PCR fragments were then subjected to SSCP analysis polyacrylamide gel electrophoresis.
Results: PCR-SSCP analysis demonstrated no mutations in the twenty-nine paired tumor samples studied.
Conclusion: This result suggests that mutations within exon four of human beta tubulin are rare in newly-diagnosed and recurrent paclitaxel resistant human ovarian cancer.