结直肠腺癌BRAF基因突变的检测及其临床意义

Detection of BRAF gene mutation and its clinical significance in colorectal cancer

目的:探讨结直肠腺癌BRAF基因突变的检测及临床意义。方法:采用PCR直接测序法检测结直肠腺癌患者石蜡包埋肿瘤组织中BRAF基因突变情况,分析BRAF基因突变与患者性别、年龄、组织学分级及临床分期的相关性。结果:17例BRAF基因突变结直肠腺癌病例中,16例为15外显子突变,1例为11外显子突变。16例中,突变位于15外显子第600位密码子14例,包括第1 799位碱基T突变为A(Val600Glu,V600E)13例(92.9%),第1 799、1 800位碱基T、G突变为A、A(Val600Glu,V600E)1例;突变位于15外显子第594位密码子2例,均为第1 780位碱基G突变为A(Asp594Asn,D594N)。1例11外显子突变位于第468位密码子,第1 403位碱基G突变为C(Gly468Va,G468V)。BRAF基因突变与患者性别、年龄无相关性;组织学分级为Ⅲ级的BRAF基因突变患者数多于Ⅱ级(P=0.029);临床分期为Ⅳ期的BRAF基因突变患者数多于Ⅱ期、Ⅲ期(P=0.011)。结论:BRAF基因突变与结直肠腺癌组织学分级和临床分期相关,随着组织学分级和临床分期的增加,BRAF基因突变率升高。

Objective:To investigate the clinical significance of BRAF gene mutation detection in colorectal cancer.Methods:The BRAF gene mutations in paraffin embedded tumor tissues of colorectal cancer patients were detected by PCR direct sequencing,and the relationship between BRAF gene mutation and gender,age,histological grade,and clinical stage was analyzed.Results:In 17 cases of colorectal cancer with BRAF gene mutations,16 cases had mutations in fifteenth exon and 1 case in eleventh exon.In 16 cases,mutations were mainly located in the 600th codon of the fifteenth exon in 14 cases,including 13 cases with the 1 799th base mutation of T to A(Val600Glu,V600E;accounting for 92.9%of the mutations in the 600th codon),and 1 case with the 1 799th and 1 800th base mutations of GT to AA(Val600Glu,V600E);2 cases in the 594th codon of fifteenth exon with the 1 780th base G to A(Asp594Asn,D594N).The mutation of eleventh exon in 1 case was in the 468th codon with the mutation of the 1 403rd base G to C(Gly468Va,G468V).The status of BRAF gene mutations was not related to the sex and age of the patient.The number of BRAF gene mutation patients with histological gradeⅢwas more than that of gradeⅡ(P=0.029)and the number of BRAF gene mutations with clinical stageⅣwas more than those with stageⅡand stageⅢ(P=0.011).Conclusions:BRAF gene mutations in colorectal cancers are associated with histological grade,clinical stage and worse prognosis.With the increase of histological grade and clinical stage,the mutation rate of BRAF gene increases.