CAJ | 학술논문

目的：探讨胃癌组织及胃癌细胞系中XPF C2169A无义突变与其发生的关系。方法对488例肿瘤患者外周血及64例胃癌组织进行基因组DNA的提取，应用Taqman MGB探针进行基因分型；应用免疫组化法检测XPF蛋白的情况。结果488例肿瘤患者外周血中C2169A无一发生突变，然而64例胃癌组织中发现32例（50％）发生突变，并导致XPF蛋白表达水平降低，羧基端失去194个氨基酸；XPF C2169A突变仅出现在癌组织中，而癌旁正常组织中没有突变；突变后表达的截断蛋白tXPF不能与ERCC1相互作用，迅速通过泛素化降解。结论胃癌中XPF C2169A主要是单等位基因突变，表明XPF是一个单倍型剂量不足修复基因，XPF C2169A突变可以作为胃癌早期诊断和治疗的靶点。
목적：탐토위암조직급위암세포계중XPF C2169A무의돌변여기발생적관계。방법대488례종류환자외주혈급64례위암조직진행기인조DNA적제취，응용Taqman MGB탐침진행기인분형；응용면역조화법검측XPF단백적정황。결과488례종류환자외주혈중C2169A무일발생돌변，연이64례위암조직중발현32례（50％）발생돌변，병도치XPF단백표체수평강저，최기단실거194개안기산；XPF C2169A돌변부출현재암조직중，이암방정상조직중몰유돌변；돌변후표체적절단단백tXPF불능여ERCC1상호작용，신속통과범소화강해。결론위암중XPF C2169A주요시단등위기인돌변，표명XPF시일개단배형제량불족수복기인，XPF C2169A돌변가이작위위암조기진단화치료적파점。
Objective To study the relation between C2169A nonsense mutation in XPF and Carcinogenesis in gastric cancer tissues and cell lines.Methods Genomic DNA was extracted from blood samples of 488 cancer patients and 64 gastric tumors.The genotype was mapped using a Taqman MGB probe.Expression of XPF was examined by immunohistochemistry.Re-sults The C2169A mutation was not detected in 488 samples of blood genomic DNA,yet was found in 32 of 64 gastric cancer tis-sue samples (50.0%) ,resulted in a 194 C-terminal amino acid loss in XPF protein and lower expression.The XPF C2169A was found in cancer tissues,but not in surrounding normal tissues.The truncated form of XPF ( tXPF) impaired interaction with ER-CC1,was rapidly degraded via ubiquitination.Conclusion In gastric cancer,the C2169A mutation is monoallelic,indicating that XPF is a haplo-insufficient DNA repair gene.The C2169A mutation might be regarded as a therapeutic target for early diagnosis and treatment of gastric cancer.