β tubulin mutations are rare in human ovarian carcinoma

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. P-32 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.