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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 1,065 - 1,076 (12page)
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Purpose The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung.
Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer.
Materials and Methods We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2mutants were confirmed by in vitro assays.
Results We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied.
One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant–bearing cells.
Conclusion Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2mutations were located in a kinase domain and induced an increase in cell proliferation rate.
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참고문헌 (29)
참고문헌 신청
Sasaki H / 2012 / DDR2 polymorphisms and mRNA expression in lung cancers of Japanese patients / Oncol Lett 4:33~37
Miao L / 2014 / Identification of novel driver mutations of the discoidin domain receptor 2(DDR2)gene in squamous cell lung cancer of Chinese patients / BMC Cancer 14:369
신애선 / 2017 / Lung Cancer Epidemiology in Korea / Cancer Research and Treatment 49(3):616~626
Ichikawa O / 2007 / Structural basis of the collagen-binding mode of discoidin domain receptor 2 / EMBO J 26:4168~4176
Terashima M / 2016 / Functional analyses of mutations in receptor tyrosine kinase genes in non-small cell lung cancer : double-edged sword of DDR2 / Clin Cancer Res 22:3663~3671
Miao L / 2014 / Identification of novel driver mutations of the discoidin domain receptor 2(DDR2)gene in squamous cell lung cancer of Chinese patients / BMC Cancer 14:369
신애선 / 2017 / Lung Cancer Epidemiology in Korea / Cancer Research and Treatment 49(3):616~626
Ichikawa O / 2007 / Structural basis of the collagen-binding mode of discoidin domain receptor 2 / EMBO J 26:4168~4176
Terashima M / 2016 / Functional analyses of mutations in receptor tyrosine kinase genes in non-small cell lung cancer : double-edged sword of DDR2 / Clin Cancer Res 22:3663~3671
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