TY - JOUR
T1 - Peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp-based detection test for gefitinib-refractory T790M epidermal growth factor receptor mutation
AU - Miyazawa, Hitoshi
AU - Tanaka, Tomoaki
AU - Nagai, Yoshiaki
AU - Matsuoka, Masaru
AU - Sutani, Akihisa
AU - Udagawa, Kiyoshi
AU - Zhang, Jialing
AU - Hirama, Takashi
AU - Murayama, Yoshitake
AU - Koyama, Nobuyuki
AU - Ikebuchi, Kenji
AU - Nagata, Makoto
AU - Kanazawa, Minoru
AU - Nukiwa, Toshihiro
AU - Takenoshita, Seiichi
AU - Kobayashi, Kunihiko
AU - Hagiwara, Koichi
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1349-7006.2007.00706.x
DO - 10.1111/j.1349-7006.2007.00706.x
M3 - Article
C2 - 18271876
AN - SCOPUS:38949177364
VL - 99
SP - 595
EP - 600
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 3
ER -