Yan Chi, Zhao Chengzhi, Yang Ke, Zhou Hongyan, Jing Limin, Zhao Weixing, Dou Wenguang, Xia Qingxin, Ma Jie, Wei Bing, Guo Yongjun
Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
Henan Key Laboratory of Molecular Pathology, Zhengzhou, China.
Front Mol Biosci. 2022 Jun 2;9:730213. doi: 10.3389/fmolb.2022.730213. eCollection 2022.
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. 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. 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. c.1926delA p.K642S*FS mutation in primary and recurrent GIST patients and c.1936T>G p.Y646D point mutation in melanoma patients in exon 13 were first demonstrated to be novel targets resistant to imatinib agent. 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.
随着克服基因突变引起的耐药性的临床药物的发展，靶向治疗在胃肠道间质瘤（GIST）和黑色素瘤中发挥着越来越重要的作用。基因突变在GIST患者中占很大比例，已知这些患者对酪氨酸激酶抑制剂敏感或耐药。然而，罕见突变在药物疗效和无进展生存期方面所起的作用仍不清楚。使用桑格测序法从GIST和黑色素瘤病例中鉴定出两种罕见突变。进一步进行细胞实验以证明它们在伊马替尼耐药中的作用。首次证明原发性和复发性GIST患者中的c.1926delA p.K642S*FS突变以及黑色素瘤患者外显子13中的c.1936T>G p.Y646D点突变是对伊马替尼耐药的新靶点。外显子13中的c.1926delA和c.1936T>G突变是对伊马替尼耐药的具有临床意义的靶点。本研究为GIST和黑色素瘤的治疗提供了指导。
