| RRC ID |
1465
|
| 著者 |
Nagai Y, Miyazawa H, Huqun, Tanaka T, Udagawa K, Kato M, Fukuyama S, Yokote A, Kobayashi K, Kanazawa M, Hagiwara K.
|
| タイトル |
Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp.
|
| ジャーナル |
Cancer Res
|
| Abstract |
Lung cancer is one of the leading causes of the cancer death worldwide. Gefitinib is an inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and has been introduced in the treatment of advanced lung cancers. The responsiveness to gefitinib has been linked to the presence of EGFR mutations. Clinical samples contain many normal cells in addition to cancer cells. A method capable of detecting EGFR mutations in a large background of wild-type EGFR genes could provide a superior clinical test. We developed a rapid and sensitive detection system for EGFR mutations named the peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp that can detect EGFR mutations in the presence of 100-to 1,000-fold background of wild-type EGFR. We used this method to screen 30 non-small cell lung cancer cell lines established from Japanese patients. In addition to 11 cell lines that have mutations, we found 12 cell lines in which specific mutations are observed only in the subpopulation(s) of the cells. Genetic heterogeneity of EGFR suggests that the EGFR gene is unstable in established cancers and the heterogeneity may explain variable clinical responses of lung cancers to gefitinib.
|
| 巻・号 |
65(16)
|
| ページ |
7276-82
|
| 公開日 |
2005-8-15
|
| DOI |
10.1158/0008-5472.CAN-05-0331
|
| PII |
65/16/7276
|
| PMID |
16105816
|
| MeSH |
Antineoplastic Agents / pharmacology
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / enzymology
Carcinoma, Non-Small-Cell Lung / genetics*
Cell Line, Tumor
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / genetics
Gefitinib
Gene Amplification
Genes, erbB-1 / genetics*
Genetic Heterogeneity
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / enzymology
Lung Neoplasms / genetics*
Mutation*
Peptide Nucleic Acids / chemistry*
Peptide Nucleic Acids / genetics
Polymerase Chain Reaction / methods*
Quinazolines / pharmacology
Sensitivity and Specificity
|
| IF |
9.727
|
| 引用数 |
395
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RERF-LC-AI(RCB0444)
LC-2/ad(RCB0440)
PC-14(RCB0446)
RERF-LC-KJ(RCB1313) |
