PMID- 18398498 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20110714 LR - 20211020 IS - 0912-0009 (Print) IS - 1880-5086 (Electronic) IS - 0912-0009 (Linking) VI - 40 IP - 3 DP - 2007 May TI - Analysis of Beta-Tubulin Gene Exon 4 Mutations in Advanced Stage III or IV Gastric Cancer. PG - 210-5 LID - 10.3164/jcbn.40.210 [doi] 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. FAU - Tahara, Tomomitsu AU - Tahara T AD - Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. FAU - Arisawa, Tomiyasu AU - Arisawa T FAU - Shibata, Tomoyuki AU - Shibata T FAU - Hirata, Ichiro AU - Hirata I FAU - Nakano, Hiroshi AU - Nakano H LA - eng PT - Journal Article PL - Japan TA - J Clin Biochem Nutr JT - Journal of clinical biochemistry and nutrition JID - 8700907 PMC - PMC2275766 OTO - NOTNLM OT - SSCP OT - beta-tubulin OT - exon 4 OT - gastric cancer OT - mutation EDAT- 2008/04/10 09:00 MHDA- 2008/04/10 09:01 PMCR- 2007/05/01 CRDT- 2008/04/10 09:00 PHST- 2006/07/31 00:00 [received] PHST- 2006/11/07 00:00 [accepted] PHST- 2008/04/10 09:00 [pubmed] PHST- 2008/04/10 09:01 [medline] PHST- 2008/04/10 09:00 [entrez] PHST- 2007/05/01 00:00 [pmc-release] AID - jcbn2007027 [pii] AID - 10.3164/jcbn.40.210 [doi] PST - ppublish SO - J Clin Biochem Nutr. 2007 May;40(3):210-5. doi: 10.3164/jcbn.40.210.