CAJ | 학술논문

目的分析胃肠间质瘤(GIST)患者服用甲磺酸伊马替尼(imatinib mesylate)前后的c-kit/PDGFRα基因型改变以及与舒尼替尼(sunitinib)临床疗效的相关性.方法收集病理确诊GIST患者甲磺酸伊马替尼治疗前以及治疗失败后的组织标本共5对,采用PCR扩增,脱氧末端终止法测序,并对比治疗前后的基因型变化,探讨甲磺酸伊马替尼的耐药机制以及后续对舒尼替尼的治疗反应.结果甲磺酸伊马替尼治疗前以及治疗失败后的GIST患者5对组织标本,原发突变为c-kit基因外显子11突变者3例,甲磺酸伊马替尼耐药后均检测到继发基因突变,其中2例为c-kit基因外显子13继发突变,分别为V654A突变和V654E突变;1例为继发c-kit基因外显子17 N822K突变,二线药物舒尼替尼治疗后,3例均为疾病稳定状态,无进展生存期分别为3.5、4.4和3.8个月.另2例原发突变为c-kit基因外显子9突变,甲磺酸伊马替尼治疗失败后均未检测到继发基因突变,二线药物舒尼替尼治疗后疗效均为部分缓解,无进展生存期分别为13.1和12.0个月,且截至最后随访期仍未进展.结论 GIST继发突变与原发突变类型可可能相关,继发耐药后的基因型与舒尼替尼疗效相关.
목적 분석위장간질류(GIST)환자복용갑광산이마체니(imatinib mesylate)전후적c-kit/PDGFRα기인형개변이급여서니체니(sunitinib)림상료효적상관성.방법 수집병리학진GIST환자갑광산이마체니치료전이급치료실패후적조직표본공5대,채용PCR확증,탈양말단종지법측서,병대비치료전후적기인형변화,탐토갑광산이마체니적내약궤제이급후속대서니체니적치료반응.결과 갑광산이마체니치료전이급치료실패후적GIST환자5대조직표본,원발돌변위c-kit기인외현자11돌변자3례,갑광산이마체니내약후균검측도계발기인돌변,기중2례위c-kit기인외현자13계발돌변,분별위V654A돌변화V654E돌변;1례위계발c-kit기인외현자17 N822K돌변,이선약물서니체니치료후,3례균위질병은정상태,무진전생존기분별위3.5、4.4화3.8개월.령2례원발돌변위c-kit기인외현자9돌변,갑광산이마체니치료실패후균미검측도계발기인돌변,이선약물서니체니치료후료효균위부분완해,무진전생존기분별위13.1화12.0개월,차절지최후수방기잉미진전.결론 GIST계발돌변여원발돌변류형가가능상관,계발내약후적기인형여서니체니료효상관.
Objective To investigate the relationship between second\ry mutdtions of c-kit/PDGFRα resistfnce to im,tinib mesyl,te and the efficacy of sunitinib in patients with gastrointestinal stromal tumor (GIST).Methods Five pairs specimens were collected before and after imatinib mesylate resistance.DNA for molecular genetic investigation was extracted from formalin-fixed,paraffin-embedded tissues.Mutational analysis was performed by using PCR and direct sequeocing.Results Five pairs of specimens were collected before and after imatinib mesylate resistance from.5 GIST patients.C-kit exon 11mutations were detected in 3 patients,which were all acquired mutations,including c-kit exon 13 V654A,c-kit exon 13 V654E and c-kit exon 17 N822K,after imatinib mesylate resistance.Furthermore,after sunitinib treatment,3 patients had stable disease and progression free survival (PFS) were 3.5 months,4.4 months and 3.8 months,respectively.C-kit exon 9 mutations were detected in 2 patients with no acquired mutations after imatinib mesylate resistance.And the both had partial response from sunitinib,following with 13.1 months and 12.0 months PFS respectively.Conclusion The c-kit/PDGFRαt genotypes after imatinib mesylate resistance may both relate to primary mutations and efficacy of sunitinib treatment.