AUTHOR=Yan Chi , Zhao Chengzhi , Yang Ke , Zhou Hongyan , Jing Limin , Zhao Weixing , Dou Wenguang , Xia Qingxin , Ma Jie , Wei Bing , Guo Yongjun
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
JOURNAL=Frontiers in Molecular Biosciences
VOLUME=9
YEAR=2022
URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.730213
DOI=10.3389/fmolb.2022.730213
ISSN=2296-889X
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.