Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments
Background: Target therapies play more and more important roles in gastrointestinal stromal tumors (GISTs) and melanoma with the advancement of clinical drugs that overcome the resistance caused by gene mutations. c-KIT gene mutations account for a large portion of GIST patients, which are known to...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.730213/full |
| _version_ | 1811233208730124288 |
|---|---|
| author | Chi Yan Chi Yan Chengzhi Zhao Chengzhi Zhao Ke Yang Ke Yang Hongyan Zhou Limin Jing Weixing Zhao Wenguang Dou Qingxin Xia Jie Ma Jie Ma Bing Wei Bing Wei Yongjun Guo Yongjun Guo |
| author_facet | Chi Yan Chi Yan Chengzhi Zhao Chengzhi Zhao Ke Yang Ke Yang Hongyan Zhou Limin Jing Weixing Zhao Wenguang Dou Qingxin Xia Jie Ma Jie Ma Bing Wei Bing Wei Yongjun Guo Yongjun Guo |
| author_sort | Chi Yan |
| collection | DOAJ |
| description | Background: Target therapies play more and more important roles in gastrointestinal stromal tumors (GISTs) and melanoma with the advancement of clinical drugs that overcome the resistance caused by gene mutations. c-KIT gene mutations account for a large portion of GIST patients, which are known to be sensitive or resistant to tyrosine kinase inhibitors. However, the role rare mutations play in drug efficacy and progression-free duration remains elusive.Methods: Two rare mutations were identified using Sanger sequencing from the GIST and melanoma cases. Cell experiments were further carried out to demonstrate their role in the imatinib resistance.Results:c-KIT c.1926delA p.K642S*FS mutation in primary and recurrent GIST patients and c-KIT c.1936T>G p.Y646D point mutation in melanoma patients in exon 13 were first demonstrated to be novel targets resistant to imatinib agent.Conclusion:c-KIT mutations c.1926delA and c.1936T>G in exon 13 are clinically significant targets that exhibit resistance to imatinib. This study provides guidance to GIST and melanoma treatments. |
| first_indexed | 2024-04-12T11:16:46Z |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T11:16:46Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-5c14ebbe31584c398310516b2c8bcc702022-12-22T03:35:28ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-06-01910.3389/fmolb.2022.730213730213Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell ExperimentsChi Yan0Chi Yan1Chengzhi Zhao2Chengzhi Zhao3Ke Yang4Ke Yang5Hongyan Zhou6Limin Jing7Weixing Zhao8Wenguang Dou9Qingxin Xia10Jie Ma11Jie Ma12Bing Wei13Bing Wei14Yongjun Guo15Yongjun Guo16Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Molecular Pathology, Zhengzhou, ChinaDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Molecular Pathology, Zhengzhou, ChinaDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Molecular Pathology, Zhengzhou, ChinaDepartment of Pathology, Xinxiang First People’s Hospital, Xinxiang, ChinaComputed Tomography Room, Xinxiang First People’s Hospital, Xinxiang, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Radiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Molecular Pathology, Zhengzhou, ChinaDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Molecular Pathology, Zhengzhou, ChinaDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaHenan Key Laboratory of Molecular Pathology, Zhengzhou, ChinaBackground: Target therapies play more and more important roles in gastrointestinal stromal tumors (GISTs) and melanoma with the advancement of clinical drugs that overcome the resistance caused by gene mutations. c-KIT gene mutations account for a large portion of GIST patients, which are known to be sensitive or resistant to tyrosine kinase inhibitors. However, the role rare mutations play in drug efficacy and progression-free duration remains elusive.Methods: Two rare mutations were identified using Sanger sequencing from the GIST and melanoma cases. Cell experiments were further carried out to demonstrate their role in the imatinib resistance.Results:c-KIT c.1926delA p.K642S*FS mutation in primary and recurrent GIST patients and c-KIT c.1936T>G p.Y646D point mutation in melanoma patients in exon 13 were first demonstrated to be novel targets resistant to imatinib agent.Conclusion:c-KIT mutations c.1926delA and c.1936T>G in exon 13 are clinically significant targets that exhibit resistance to imatinib. This study provides guidance to GIST and melanoma treatments.https://www.frontiersin.org/articles/10.3389/fmolb.2022.730213/fullGISTc-KITmelanomarare mutationsimatinib resistance |
| spellingShingle | Chi Yan Chi Yan Chengzhi Zhao Chengzhi Zhao Ke Yang Ke Yang Hongyan Zhou Limin Jing Weixing Zhao Wenguang Dou Qingxin Xia Jie Ma Jie Ma Bing Wei Bing Wei Yongjun Guo Yongjun Guo Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments Frontiers in Molecular Biosciences GIST c-KIT melanoma rare mutations imatinib resistance |
| title | Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments |
| title_full | Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments |
| title_fullStr | Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments |
| title_full_unstemmed | Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments |
| title_short | Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments |
| title_sort | rare c kit c 1926dela and c 1936t g mutations in exon 13 define imatinib resistance in gastrointestinal stromal tumors and melanoma patients case reports and cell experiments |
| topic | GIST c-KIT melanoma rare mutations imatinib resistance |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.730213/full |
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