Absence of beta-tubulin gene mutation in gastric carcinoma.
BACKGROUND
Effective chemotherapy for advanced gastric cancer is yet to be established. Taxanes, novel anticancer drugs which bind to beta-tubulin and prevent disruption of microtubules, are newly approved and promising agents for advanced and recurrent gastric cancer. To predict the chemoresistance to a taxan in gastric cancer, we examined the genetic mutations of the beta-tubulin gene.


METHODS
Fifty pairs of gastric tumor and normal mucosa tissues were obtained from operations and the genomic DNA was extracted from each specimen. The four exons of the beta-tubulin gene were amplified for DNA mutations by single-strand conformation polymorphism (SSCP) methods and sequencing analysis.


RESULTS
Nine (18%) of 50 patients with gastric cancer had two kinds of silent variations of the beta-tubulin gene in exon 4. Three kinds of intronic variations were detected in exons 1, 2, and 3. However, no genetic alterations that would change the beta-tubulin protein structure were detected in any of the 50 gastric tumors.


CONCLUSIONS
Our findings indicate that mutations of the beta-tubulin gene, which might be a contraindication for chemotherapy based on taxans, were very rare events in gastric cancer.
Urano
Naomi
N
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka (E-2), Suita, Osaka 565-0871, Japan.
Fujiwara
Yoshiyuki
Y
Hasegawa
Seiichi
S
Miyoshi
Yasuo
Y
Noguchi
Shinzaburo
S
Takiguchi
Shuji
S
Yasuda
Takushi
T
Yano
Masahiko
M
Monden
Morito
M
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D003062:Codon / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005091:Exons / Q000187:drug effects / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007438:Introns / Q000187:drug effects / Q000235:genetics; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*; D043823:Taxoids / Q000627:therapeutic use; D014404:Tubulin / Q000187:drug effects / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D003062:Codon; D043823:Taxoids; D014404:Tubulin; D017239:Paclitaxel