EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma
Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Ton...
Ausführliche Beschreibung
Autor*in: |
Memon AA [verfasserIn] Zhang HP [verfasserIn] Gu Y [verfasserIn] Luo Q [verfasserIn] Shi JJ [verfasserIn] Deng Z [verfasserIn] Ma J [verfasserIn] Ma W [verfasserIn] |
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2017 |
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In: OncoTargets and Therapy - Dove Medical Press, 2009, (2017), Seite 4607-4613 |
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year:2017 ; pages:4607-4613 |
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DOAJ056154321 |
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(DE-627)DOAJ056154321 (DE-599)DOAJ9971e369c0fe4167802ab6d54090b04d DE-627 ger DE-627 rakwb eng RC254-282 Memon AA verfasserin aut EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors Lung Squamous Carcinoma EGFR exon 19 Mutation Profile PCR-DGGE Tyrosine Kinase Inhibitors. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zhang HP verfasserin aut Gu Y verfasserin aut Luo Q verfasserin aut Shi JJ verfasserin aut Deng Z verfasserin aut Ma J verfasserin aut Ma W verfasserin aut In OncoTargets and Therapy Dove Medical Press, 2009 (2017), Seite 4607-4613 (DE-627)600307654 (DE-600)2495130-4 11786930 nnns year:2017 pages:4607-4613 https://doaj.org/article/9971e369c0fe4167802ab6d54090b04d kostenfrei https://www.dovepress.com/egfr-with-tki-sensitive-mutations-in-exon-19-is-highly-expressed-and-f-peer-reviewed-article-OTT kostenfrei https://doaj.org/toc/1178-6930 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2017 4607-4613 |
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(DE-627)DOAJ056154321 (DE-599)DOAJ9971e369c0fe4167802ab6d54090b04d DE-627 ger DE-627 rakwb eng RC254-282 Memon AA verfasserin aut EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors Lung Squamous Carcinoma EGFR exon 19 Mutation Profile PCR-DGGE Tyrosine Kinase Inhibitors. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zhang HP verfasserin aut Gu Y verfasserin aut Luo Q verfasserin aut Shi JJ verfasserin aut Deng Z verfasserin aut Ma J verfasserin aut Ma W verfasserin aut In OncoTargets and Therapy Dove Medical Press, 2009 (2017), Seite 4607-4613 (DE-627)600307654 (DE-600)2495130-4 11786930 nnns year:2017 pages:4607-4613 https://doaj.org/article/9971e369c0fe4167802ab6d54090b04d kostenfrei https://www.dovepress.com/egfr-with-tki-sensitive-mutations-in-exon-19-is-highly-expressed-and-f-peer-reviewed-article-OTT kostenfrei https://doaj.org/toc/1178-6930 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2017 4607-4613 |
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(DE-627)DOAJ056154321 (DE-599)DOAJ9971e369c0fe4167802ab6d54090b04d DE-627 ger DE-627 rakwb eng RC254-282 Memon AA verfasserin aut EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors Lung Squamous Carcinoma EGFR exon 19 Mutation Profile PCR-DGGE Tyrosine Kinase Inhibitors. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zhang HP verfasserin aut Gu Y verfasserin aut Luo Q verfasserin aut Shi JJ verfasserin aut Deng Z verfasserin aut Ma J verfasserin aut Ma W verfasserin aut In OncoTargets and Therapy Dove Medical Press, 2009 (2017), Seite 4607-4613 (DE-627)600307654 (DE-600)2495130-4 11786930 nnns year:2017 pages:4607-4613 https://doaj.org/article/9971e369c0fe4167802ab6d54090b04d kostenfrei https://www.dovepress.com/egfr-with-tki-sensitive-mutations-in-exon-19-is-highly-expressed-and-f-peer-reviewed-article-OTT kostenfrei https://doaj.org/toc/1178-6930 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2017 4607-4613 |
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(DE-627)DOAJ056154321 (DE-599)DOAJ9971e369c0fe4167802ab6d54090b04d DE-627 ger DE-627 rakwb eng RC254-282 Memon AA verfasserin aut EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors Lung Squamous Carcinoma EGFR exon 19 Mutation Profile PCR-DGGE Tyrosine Kinase Inhibitors. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zhang HP verfasserin aut Gu Y verfasserin aut Luo Q verfasserin aut Shi JJ verfasserin aut Deng Z verfasserin aut Ma J verfasserin aut Ma W verfasserin aut In OncoTargets and Therapy Dove Medical Press, 2009 (2017), Seite 4607-4613 (DE-627)600307654 (DE-600)2495130-4 11786930 nnns year:2017 pages:4607-4613 https://doaj.org/article/9971e369c0fe4167802ab6d54090b04d kostenfrei https://www.dovepress.com/egfr-with-tki-sensitive-mutations-in-exon-19-is-highly-expressed-and-f-peer-reviewed-article-OTT kostenfrei https://doaj.org/toc/1178-6930 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2017 4607-4613 |
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EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma |
abstract |
Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors |
abstractGer |
Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors |
abstract_unstemmed |
Aadil Ahmed Memon,1 Haiping Zhang,2 Ye Gu,3 Qian Luo,4 Jiajun Shi,1 Zixin Deng,1 Jian Ma,5 Wei Ma1 1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 2Oncology Department, 3Endoscope Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 4Core Facility and Technical Service Center, School of Life Science and Biotechnology, Shanghai Jiao Tong University, 5Pneumology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Abstract: Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed. Keywords: lung squamous carcinoma, EGFR exon 19, mutation profile, PCR-DGGE, tyrosine kinase inhibitors |
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EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma |
url |
https://doaj.org/article/9971e369c0fe4167802ab6d54090b04d https://www.dovepress.com/egfr-with-tki-sensitive-mutations-in-exon-19-is-highly-expressed-and-f-peer-reviewed-article-OTT https://doaj.org/toc/1178-6930 |
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