CAJ | 학술논문

目的：观察结直肠癌患者肿瘤组织中KRAS和BRAF基因的突变情况，并分析其与患者临床病理特征的关系。方法经病理检查确诊的结直肠癌患者100例，留取手术切除的肿瘤组织标本，采用直接测序法检测其中的KRAS基因外显子2第12、13位密码子以及BRAF基因外显子15的突变状态，分析基因突变与患者临床病理特征的关系。结果本组患者KRAS、BRAF基因突变率分别为28％（28／100）、5％（5／100），BRAF基因在KRAS野生型患者中的突变率为5．6％（4／72）。 KRAS基因突变类型共有8种，以G12D、G12V及G13D最常见；BRAF基因突变类型共有3种，以V600 E最常见。 KRAS基因在≥60岁患者中的突变率高于＜60岁患者（ P＜0．05），且在肿瘤原发灶分化程度较高的患者中突变率高（ P＜0．05）；而BRAF基因在肝转移灶直径越大的患者中突变率升高越明显（P＜0．05）。 KRAS及BRAF基因突变与原发灶部位均有关（P均＜0．05）。结论结直肠癌患者肿瘤组织中KRAS基因突变率较高， KRAS基因突变与患者年龄、原发灶组织学分级、肝外侵犯或转移及原发灶部位相关，而BRAF基因突变与肝转移灶最大直径和原发灶部位有关。
목적：관찰결직장암환자종류조직중KRAS화BRAF기인적돌변정황，병분석기여환자림상병리특정적관계。방법경병리검사학진적결직장암환자100례，류취수술절제적종류조직표본，채용직접측서법검측기중적KRAS기인외현자2제12、13위밀마자이급BRAF기인외현자15적돌변상태，분석기인돌변여환자림상병리특정적관계。결과본조환자KRAS、BRAF기인돌변솔분별위28％（28／100）、5％（5／100），BRAF기인재KRAS야생형환자중적돌변솔위5．6％（4／72）。 KRAS기인돌변류형공유8충，이G12D、G12V급G13D최상견；BRAF기인돌변류형공유3충，이V600 E최상견。 KRAS기인재≥60세환자중적돌변솔고우＜60세환자（ P＜0．05），차재종류원발조분화정도교고적환자중돌변솔고（ P＜0．05）；이BRAF기인재간전이조직경월대적환자중돌변솔승고월명현（P＜0．05）。 KRAS급BRAF기인돌변여원발조부위균유관（P균＜0．05）。결론결직장암환자종류조직중KRAS기인돌변솔교고， KRAS기인돌변여환자년령、원발조조직학분급、간외침범혹전이급원발조부위상관，이BRAF기인돌변여간전이조최대직경화원발조부위유관。
Objective To observe KRAS , BRAF gene mutational status in tumor tissues of colorectal cancer patients and to analyze the correlation between mutation and clinicopathological feature .Methods Collected surgical removed tumor tissue samples from 100 cases of colorectal cancer patients , which were diagnosed by histological examination .Codons 12, 13 on exons 2 of KRAS genes and exons 15 of BRAF genes were detected by PCR-direct sequencing , to certificate the association between gene mutation and clinicopathological feature of patients .Results KRAS and BRAF mutations were present in 28%(28/100) and 5%(5/100) of patients, respectively.5.6%(4/72) samples were observed in mutation in wild-type BRAF patients.There were 8 types of mutation on KRAS genes , which were most common as G12D, G12V and G13D.Whereas, the BRAF gene mutation had 3 types and V600E was considered as the most prominent one .Mutation rate of KRAS genes was certificated higher in group of olds aged over 60 years than the rest(P<0.05).In addition, a significant increase mutation rate occurred in patients with primary tumors in high differentiation and extrahepatic invasion or metastasis ( P<0.05) .How-ever, BRAF genes mutation rate obviously increased in patients with bigger diameter of liver metastatic lesions (P<0.05). KRAS and BRAF gene mutations were in association with primary tumor sites (all P<0.05).Conclusion There is a higher mutation rate on KRAS genes in tumor tissues of colorectal cancer patients , which is considered as in relation to factors of age, histological grade of primary tumor , extrahepatic invasion or metastasis and primary site .Mutation of BRAF genes is as-sociated with the maximum diameter of liver metastasis and primary tumor sites .