beta-Tubulin mutations in ovarian cancer using single strand conformation analysis-risk of false positive results from paraffin embedded tissues.
Mutations in the beta-tubulin gene have been proposed as a resistance mechanism to paclitaxel. We therefore investigated the presence of mutations in the beta-tubulin M40 gene in 40 ovarian tumours (16 paraffin-embedded and 24 freshly frozen) selected for good or poor response to chemotherapy with paclitaxel or non-tubulin-affecting regimens. The presence of mutations was investigated using single strand conformation analysis followed by sequencing of the products with altered mobility. No sequence variants in the exons of the beta-tubulin M40 gene were detected. Non-reproducible shifts were identified, in eight out of 16 paraffin embedded samples. This may explain some of the previously published discrepancies. In conclusion, sequence variants in the beta-tubulin M40 gene are rare and are unlikely to be a clinically relevant explanation of resistance to paclitaxel.
Gréen
Henrik
H
Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. henrick.green@imv.liu.se
Rosenberg
Per
P
Söderkvist
Peter
P
Horvath
György
G
Peterson
Curt
C
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D005629:Frozen Sections; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use; D016612:Paraffin Embedding; D018807:Polymorphism, Single-Stranded Conformational; D014404:Tubulin / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D014404:Tubulin; D017239:Paclitaxel