抄録
The mechanisms that cause chemoresistance of gastric cancer have yet to be elucidated. Taxanes and promising agents that were recently approved for treatment of advanced or recurrent gastric cancer. Mutations of beta-tubulin, which is a target of taxianes, have been shown to confer chemoresistance against these agents. The aim of the present study is to investigate the presence of mutations of the beta-tubulin in gastric cancer tissues. Sixty-six patients with advanced stage III or IV gastric cancer patients enrolled in this study. Paired samples of gastric cancer tissue and normal mucosa were obtained by endoscopy. The guanosine 5′-triphosphate (GTP)-binding site in exon 4 of the beta-tubulin gene was examined by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis, followed by sequencing of the products with abnormally shifted bands. SSCP analysis showed abnormal bands upstream of the GTP-binding site in 7 of the 66 patients, but sequence analysis found no nucleotide substitutions in these patients. Three variant bands were also detected down stream of the the GTP-binding site, but the sequences of the 3 products corresponded to those of two independent pseudogenes. Thus, none of the tumor samples showed mutation of the beta-tubulin exon 4 GTP-binding site. In conclusion, these findings suggest that mutations of the beta-tubulin gene are rare and are unlikely to be an important cause of taxane resistance to taxians.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 210-215 |
| ページ数 | 6 |
| ジャーナル | Journal of Clinical Biochemistry and Nutrition |
| 巻 | 40 |
| 発行部数 | 3 |
| DOI | |
| 出版物ステータス | Published - 01-05-2007 |
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All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Nutrition and Dietetics
- Clinical Biochemistry
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Analysis of beta-tubulin gene exon 4 mutations in advanced stage III or IV gastric cancer. / Tahara, Tomomitsu; Arisawa, Tomiyasu; Shibata, Tomoyuki; Hirata, Ichiro; Nakano, Hiroshi.
：: Journal of Clinical Biochemistry and Nutrition, 巻 40, 番号 3, 01.05.2007, p. 210-215.研究成果: Article
TY - JOUR
T1 - Analysis of beta-tubulin gene exon 4 mutations in advanced stage III or IV gastric cancer
AU - Tahara, Tomomitsu
AU - Arisawa, Tomiyasu
AU - Shibata, Tomoyuki
AU - Hirata, Ichiro
AU - Nakano, Hiroshi
PY - 2007/5/1
Y1 - 2007/5/1
N2 - The mechanisms that cause chemoresistance of gastric cancer have yet to be elucidated. Taxanes and promising agents that were recently approved for treatment of advanced or recurrent gastric cancer. Mutations of beta-tubulin, which is a target of taxianes, have been shown to confer chemoresistance against these agents. The aim of the present study is to investigate the presence of mutations of the beta-tubulin in gastric cancer tissues. Sixty-six patients with advanced stage III or IV gastric cancer patients enrolled in this study. Paired samples of gastric cancer tissue and normal mucosa were obtained by endoscopy. The guanosine 5′-triphosphate (GTP)-binding site in exon 4 of the beta-tubulin gene was examined by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis, followed by sequencing of the products with abnormally shifted bands. SSCP analysis showed abnormal bands upstream of the GTP-binding site in 7 of the 66 patients, but sequence analysis found no nucleotide substitutions in these patients. Three variant bands were also detected down stream of the the GTP-binding site, but the sequences of the 3 products corresponded to those of two independent pseudogenes. Thus, none of the tumor samples showed mutation of the beta-tubulin exon 4 GTP-binding site. In conclusion, these findings suggest that mutations of the beta-tubulin gene are rare and are unlikely to be an important cause of taxane resistance to taxians.
AB - The mechanisms that cause chemoresistance of gastric cancer have yet to be elucidated. Taxanes and promising agents that were recently approved for treatment of advanced or recurrent gastric cancer. Mutations of beta-tubulin, which is a target of taxianes, have been shown to confer chemoresistance against these agents. The aim of the present study is to investigate the presence of mutations of the beta-tubulin in gastric cancer tissues. Sixty-six patients with advanced stage III or IV gastric cancer patients enrolled in this study. Paired samples of gastric cancer tissue and normal mucosa were obtained by endoscopy. The guanosine 5′-triphosphate (GTP)-binding site in exon 4 of the beta-tubulin gene was examined by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis, followed by sequencing of the products with abnormally shifted bands. SSCP analysis showed abnormal bands upstream of the GTP-binding site in 7 of the 66 patients, but sequence analysis found no nucleotide substitutions in these patients. Three variant bands were also detected down stream of the the GTP-binding site, but the sequences of the 3 products corresponded to those of two independent pseudogenes. Thus, none of the tumor samples showed mutation of the beta-tubulin exon 4 GTP-binding site. In conclusion, these findings suggest that mutations of the beta-tubulin gene are rare and are unlikely to be an important cause of taxane resistance to taxians.
UR - http://www.scopus.com/inward/record.url?scp=34250829689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250829689&partnerID=8YFLogxK
U2 - 10.3164/jcbn.40.210
DO - 10.3164/jcbn.40.210
M3 - Article
C2 - 18398498
AN - SCOPUS:34250829689
VL - 40
SP - 210
EP - 215
JO - Journal of Clinical Biochemistry and Nutrition
JF - Journal of Clinical Biochemistry and Nutrition
SN - 0912-0009
IS - 3
ER -