Analysis of beta-tubulin gene alteration in human lung cancer cell lines.
We examined lung cancer cell lines for the presence of beta-tubulin gene alteration based on a previous report of a relationship between frequent beta-tubulin gene mutation in non-small-cell lung cancer and clinical response to taxanes as well as the prognosis. The mutation was defined by analyzing genomic DNA from 31 lung cancer cell lines by direct genomic sequencing using specific primers for the beta-tubulin class I gene. We detected only three genetic alterations at nonsplice sites in two introns, and a silent genetic alteration at codon 217 in exon 4. The mutation of the beta-tubulin gene was rare; moreover, these genetic alterations were predicted to evoke no biological alteration of the cancer cells. Our data suggest that the beta-tubulin gene mutation does not play a major role in the genetic mechanism of resistance to taxanes. In addition, the presence of a closely related family of beta-tubulins or pseudogenes was thought to hinder accurate evaluation of the beta-tubulin gene.
Achiwa
Hiroyuki
H
Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. h-achiwa@med.nagoya-cu.ac.jp
Sato
Shigeki
S
Shimizu
Shigeki
S
Maeda
Hiroyoshi
H
Niimi
Takashi
T
Takahashi
Takashi
T
Ueda
Ryuzo
R
Mitsudomi
Tetsuya
T
D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014404:Tubulin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D003062:Codon; D017931:DNA Primers; D014404:Tubulin