1. Academic Validation
  2. 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

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

  • Front Mol Biosci. 2022 Jun 2;9:730213. doi: 10.3389/fmolb.2022.730213.
Chi Yan 1 2 Chengzhi Zhao 1 2 Ke Yang 1 2 Hongyan Zhou 3 Limin Jing 4 Weixing Zhao 5 Wenguang Dou 6 Qingxin Xia 7 Jie Ma 1 2 Bing Wei 1 2 Yongjun Guo 1 2
Affiliations

Affiliations

  • 1 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
  • 2 Henan Key Laboratory of Molecular Pathology, Zhengzhou, China.
  • 3 Department of Pathology, Xinxiang First People's Hospital, Xinxiang, China.
  • 4 Computed Tomography Room, Xinxiang First People's Hospital, Xinxiang, China.
  • 5 Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
  • 6 Department of Radiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
  • 7 Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
Abstract

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.

Keywords

GIST; c-KIT; imatinib resistance; melanoma; rare mutations.

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