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Mutational Analysis Of The β-tubulin Gene In Lung Cancer

J. Tsurutani, T. Komiya, H. Uejima, H. Tada, Negoro Syunichi, M. Oka, S. Kohno, M. Fukuoka, K. Nakagawa
Published 2002 · Biology

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Recently, several studies have suggested that a major mechanism of resistance to paclitaxel might involve mutations in the β-tubulin gene in tumor cells. To investigate the frequency of β-tubulin mutations in Japanese patients with small and non-small cell lung cancer, direct sequence analysis following reverse transcription-polymerase chain reaction (RT-PCR) of the β-tubulin gene was performed using total RNA from 20 lung cancer cell lines and 22 specimens from lung cancer patients. First-strand cDNA sequence analysis of the 42 samples showed silent mutations at codon 180 of the β-tubulin gene, which encodes the GTP-binding site of the protein, and codons 195 and 217. However, neither missense nor non-sense mutations affecting microtubule dynamics, within or near the GTP-binding site of the β-tubulin gene, were detected. These results indicate that β-tubulin gene mutations might not play a major role in the mechanism of resistance to paclitaxel in Japanese lung cancer patients. Further investigations are needed to clarify the mechanism of drug resistance.
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