摘要目的 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.

abstractsObjective 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.