High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan

Shiu Feng Huang, Hui Ping Liu, Ling Hui Li, Yuan Chieh Ku, Yu Ning Fu, Hsien Yu Tsai, Ya Ting Chen, Yung Feng Lin, Wen Cheng Chang, Han Pin Kuo, Yi Cheng Wu, Yi Rong Chen, Shih Feng Tsai

研究成果: 雜誌貢獻文章

478 引文 (Scopus)

摘要

Purpose: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. Experimental Design: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. Results: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. Conclusions: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.
原文英語
頁(從 - 到)8195-8203
頁數9
期刊Clinical Cancer Research
10
發行號24
DOIs
出版狀態已發佈 - 十二月 15 2004
對外發佈Yes

指紋

Taiwan
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
Adenocarcinoma
Mutation Rate
Neoplasms
Exons
gefitinib
Adenosquamous Carcinoma
erbB-1 Genes
Nonsense Codon
Paraffin
Squamous Cell Carcinoma
Decision Making
Carcinogenesis
Research Design
Phosphotransferases
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. / Huang, Shiu Feng; Liu, Hui Ping; Li, Ling Hui; Ku, Yuan Chieh; Fu, Yu Ning; Tsai, Hsien Yu; Chen, Ya Ting; Lin, Yung Feng; Chang, Wen Cheng; Kuo, Han Pin; Wu, Yi Cheng; Chen, Yi Rong; Tsai, Shih Feng.

於: Clinical Cancer Research, 卷 10, 編號 24, 15.12.2004, p. 8195-8203.

研究成果: 雜誌貢獻文章

Huang, SF, Liu, HP, Li, LH, Ku, YC, Fu, YN, Tsai, HY, Chen, YT, Lin, YF, Chang, WC, Kuo, HP, Wu, YC, Chen, YR & Tsai, SF 2004, 'High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan', Clinical Cancer Research, 卷 10, 編號 24, 頁 8195-8203. https://doi.org/10.1158/1078-0432.CCR-04-1245
Huang, Shiu Feng ; Liu, Hui Ping ; Li, Ling Hui ; Ku, Yuan Chieh ; Fu, Yu Ning ; Tsai, Hsien Yu ; Chen, Ya Ting ; Lin, Yung Feng ; Chang, Wen Cheng ; Kuo, Han Pin ; Wu, Yi Cheng ; Chen, Yi Rong ; Tsai, Shih Feng. / High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. 於: Clinical Cancer Research. 2004 ; 卷 10, 編號 24. 頁 8195-8203.
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title = "High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan",
abstract = "Purpose: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. Experimental Design: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. Results: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55{\%} (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. Conclusions: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.",
author = "Huang, {Shiu Feng} and Liu, {Hui Ping} and Li, {Ling Hui} and Ku, {Yuan Chieh} and Fu, {Yu Ning} and Tsai, {Hsien Yu} and Chen, {Ya Ting} and Lin, {Yung Feng} and Chang, {Wen Cheng} and Kuo, {Han Pin} and Wu, {Yi Cheng} and Chen, {Yi Rong} and Tsai, {Shih Feng}",
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T1 - High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan

AU - Huang, Shiu Feng

AU - Liu, Hui Ping

AU - Li, Ling Hui

AU - Ku, Yuan Chieh

AU - Fu, Yu Ning

AU - Tsai, Hsien Yu

AU - Chen, Ya Ting

AU - Lin, Yung Feng

AU - Chang, Wen Cheng

AU - Kuo, Han Pin

AU - Wu, Yi Cheng

AU - Chen, Yi Rong

AU - Tsai, Shih Feng

PY - 2004/12/15

Y1 - 2004/12/15

N2 - Purpose: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. Experimental Design: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. Results: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. Conclusions: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

AB - Purpose: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. Experimental Design: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. Results: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. Conclusions: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

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