title: Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.
abstract: Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy. A quick and sensitive method with large throughput is required to utilize the information to determine whether the molecular targeted therapy should be applied for the particular NSCLC patients. Using probes for the 13 different mutations including 11 that have already been reported, we have genotyped the EGFR mutation status in 94 NSCLC patients using the TaqMan PCR assay. We have also genotyped the EGFR mutations status in additional 182 NSCLC patients, as well as 63 gastric, 95 esophagus and 70 colon carcinoma patients. In 94 NSCLC samples, the result of the TaqMan PCR assay perfectly matched with that of the sequencing excluding one patient. In one sample in which no EGFR mutation was detected by direct sequencing, the TaqMan PCR assay detected a mutation. This patient was a gefitinib responder. In a serial dilution study, the assay could detect a mutant sample diluted in 1/10 with a wild-type sample. Of 182 NSCLC samples, 46 mutations were detected. EGFR mutation was significantly correlated with gender, smoking status, pathological subtypes, and differentiation of lung cancers. There was no mutation detected by the TaqMan PCR assay in gastric, esophagus and colon carcinomas. TaqMan PCR assay is a rapid and sensitive method of detection of EGFR mutations with high throughput, and may be useful to determine whether gefitinib should be offered for the treatment of NSCLC patients. The TaqMan PCR assay can offer us a complementary and confirmative test.
authors.affiliation: Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Endo
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Konishi
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Takada
authors.forename: Hisaichi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawahara
authors.forename: Hironori
authors.initials: H
authors.lastname: Sugiura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fukai
authors.forename: Akihide
authors.initials: A
authors.lastname: Matsumura
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Mizuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Haneda
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Keiji
authors.initials: K
authors.lastname: Iuchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D004938:Esophageal Neoplasms / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D011799:Quinazolines / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib