RRC ID 43271
著者 Miyazawa H, Tanaka T, Nagai Y, Matsuoka M, Huqun, Sutani A, Udagawa K, Zhang J, Hirama T, Murayama Y, Koyama N, Ikebuchi K, Nagata M, Kanazawa M, Nukiwa T, Takenoshita S, Kobayashi K, Hagiwara K.
タイトル Peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp-based detection test for gefitinib-refractory T790M epidermal growth factor receptor mutation.
ジャーナル Cancer Sci
Abstract Mutations in the epidermal growth factor receptor (EGFR) are observed in a fraction of non-small-cell lung cancers (NSCLS). EGFR mutation-positive NSCLS responds to gefitinib. Secondary T790M mutation confers gefitinib resistance to NSCLS. A detection test for the T790M mutation was designed based on the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. The specificity and sensitivity of the test were both greater than 0.99. The test revealed that only a small population of the PC-13 cells carried the T790M mutation. The test also revealed that the T790M mutation was found in none of 151 NSCLC specimens obtained before gefitinib treatment, whereas it was found in four of four specimens obtained from NSCLS that had become refractory to gefitinib. In one patient in whom the L858R-positive EGFR allele was amplified to multiple copies, an L858R-T790M double-mutant allele emerged during the gefitinib therapy. This allele was expressed highly. The T790M mutation detection test based on the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method is sensitive and specific, and is applicable to clinical practice. It detects T790M-positive cells in the course of gefitinib treatment, and thus will help to devise therapies effective for T790M-positive NSCLS.
巻・号 99(3)
ページ 595-600
公開日 2008-3-1
DOI 10.1111/j.1349-7006.2007.00706.x
PII CAS706
PMID 18271876
MeSH Antineoplastic Agents / therapeutic use* Base Sequence Carcinoma, Non-Small-Cell Lung / drug therapy* Carcinoma, Non-Small-Cell Lung / genetics Cell Line, Tumor DNA Mutational Analysis / methods* Drug Resistance, Neoplasm / genetics ErbB Receptors / genetics* Gefitinib Humans Lung Neoplasms / drug therapy* Lung Neoplasms / genetics* Molecular Sequence Data Oligonucleotides / chemistry Peptide Nucleic Acids / chemistry Point Mutation* Polymerase Chain Reaction / methods* Quinazolines / therapeutic use* Sensitivity and Specificity
IF 4.966
引用数 58
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 LC-2/ad(RCB0440) PC-14(RCB0446) RERF-LC-AI(RCB0444)