直乙交界处肠癌患者KRAS和BRAF基因突变138例分析  

Clinicopathological characteristics of KRAS and BRAF mutation in 138 patients with rectosigmoid cancer

作　　者：杨帆[1] 蔡业丰 金浪平 张筱骅[2] 瞿金妙[2] 

机构地区：[1]温州医科大学研究生院,浙江温州325035 [2]温州医科大学附属第一医院肿瘤外科,浙江温州325015

出　　处：《温州医科大学学报》2015年第9期646-651,655,共7页Journal of Wenzhou Medical University

基　　金：温州市科技计划资助项目(Y20140132)

摘　　要：目的:检测直乙交界处肠癌患者KRAS和BRAF基因的突变特征,分析KRAS和BRAF突变与患者临床病理特征的相关性及其临床意义。方法:收集138例直乙交界处肠癌患者的肿瘤组织,运用直接测序法检测组织标本中KRAS基因外显子2第12、第13位密码子,外显子3第61位密码子以及BRAF基因外显子15的突变状态,分析该2个基因突变与临床病理特征的相关性。结果:138例样本中,KRAS和BRAF的突变率为34.05%(47/138)和5.07%(7/138)。KRAS基因有9种突变类型,其中包括1种全新的突变类型。BRAF基因全为V600E突变。在直乙交界处肠癌患者中,KRAS基因在男性(P=0.041)、远处转移(P=0.002)、高临床分期(P=0.047)的患者中突变率更高,BRAF基因突变更常见于肿瘤多发(P=0.003)、低分化(P<0.001)的患者中,KRAS和BRAF与年龄、肿块大小、肿瘤病理形态、病理类型、浸润深度、淋巴结转移、脉管浸润、神经浸润等临床病理特征均无显著相关性。结论:直乙交界处肠癌有它的特殊性,KRAS基因在男性、远处转移、临床分期晚期的患者中突变率更高,BRAF基因在多发、低分化的患者中突变率更高。KRAS、BRAF基因在不同部位的结直肠癌中改变情况并不一致。Objective：To identify the mutation rate and mutation feature of KRAS and BRAF gene in patients with rectosigmoid carcinoma,to analyse the association between KRAS/BRAF mutations and patients＇ clinicopathological characteristics,and discuss the clinical significance of KRAS/BRAF mutations.Methods：138 patients with rectosigmoid carcinoma were collected.DNA sequencing was used to detect mutations in KRAS（codons12,13 of exon2 and codons 61 of exon3） and BRAF（exon15）.Statistically analyzing the relationships between gene mutations and clinicopathological characteristic.Results：In 138 cases,the mutation rate of KRAS and BRAF was 34.05%（47/138） and 5.07%（7/138）.9 mutation types were found in KRAS,including a new mutation type.BRAF mutation was all belong to V600 E mutation.In patients with rectosigmoid carcinoma,KRAS mutation rate was higher in male（P=0.041）,distant metastasis（P=0.002） and high clinical stages（P=0.047）.BRAF mutation rate was higher in multiple（P=0.003） and poorly differentiate（P=0.001） carcinoma.No significant associations were observed between KRAS/BRAF mutations and age,tumor size,pathomorphism,pathological type,depth of invasion,lymph node metastasis,vessel infiltration and nervous infiltration（P〈0.05）.Conclusion：Rectosigmoid carcinoma is unique.KRAS mutation rate is higher in male,distant metastasis and high clinical stages carcinoma.BRAF mutation rate is higher in multiple and poorly differentiate carcinoma.KRAS and BRAF mutations are variant in different location of colorectal cancer.

关 键 词：直乙交界 肠肿瘤 临床病理特征 KRAS基因 BRAF基因 

分 类 号：R735.3[医药卫生—肿瘤]