晚期结直肠癌患者癌组织K-ras、BRAF基因突变情况观察

K-ras and BRAF gene mutations in cancer tissues of patients with advanced colorectal cancer

目的观察晚期结直肠癌患者癌组织K-ras、BRAF基因的突变情况。方法 86例晚期(Ⅳ期)结直肠癌患者的癌组织标本,PCR法对K-ras、BRAF基因进行检测,分析K-ras、BRAF基因突变情况。结果 86例晚期结直肠癌患者癌组织的K-ras突变率为41. 8%(36/86)。36例癌组织K-ras突变中,12密码子突变的有30例,其中12密码子GGT> GAT(G12D)者10例、12密码子GGT> GTT(G12V)者7例、12密码子GGT> AGT(G12S)者6例、12密码子GGT> TGT(G12C)者5例、12密码子GGT> GCT(G12A)者2例; 13密码子突变的有6例,均为13密码子GGC> GAC(G13D)者。86例晚期结直肠癌患者癌组织BRAF突变率4. 7%(4/86),4例突变者均为密码子600GTG> GAG(V600E)者。K-ras基因突变与晚期结直肠癌患者的发病部位、肿瘤分化程度、脉管癌栓及神经侵犯、淋巴转移、肝转移有关,与年龄、浸润深度、CEA水平均无关(P均> 0. 05),BRAF基因突变与晚期结直肠癌患者的浸润深度、发病部位有关(P均<0. 05),与肿瘤分化程度、淋巴转移、脉管癌栓及神经侵犯、肝转移、年龄、CEA水平无关(P均> 0. 05)。结论晚期结直肠癌患者癌组织K-ras基因突变率较高,且以点突变为主,主要为第2外显子的第12密码子突变。晚期结直肠癌患者癌组织BRAF基因突变均为V600E突变。K-ras、BRAF基因突变可能在晚期结直肠癌的发生、发展中起重要作用。

ObjectiveTo observe the mutations of K-ras and BRAF genes in the cancer tissues of patients with advanced colorectal cancer.MethodsK-ras and BRAF genes were detected by PCR in the cancer tissues from 86 patients with advanced colorectal cancer(stage IV),and the mutations of K-ras and BRAF genes were analyzed.ResultsThe K-ras mutation rate of the cancer tissues in 86 patients with advanced colorectal cancer was 41.8%(36/86).Among 36 cases of K-ras mutation in the cancer tissues,there were 30 cases of codon 12 mutation,including 10 cases of codon 12 GGT>GAT(G12D),7 cases of codon 12 GGT>GTT(G12V),6 cases of codon 12 GGT>AGT(G12S),5 cases of codon 12 GGT>TGT(G12C),and 2 cases of codon 12 GGT>GCT(G12A);there were 6 cases of codon 13 mutation,all of which were codon 13 GGC>GAC(G13D).The BRAF mutation rate of the cancer tissues in 86 patients with advanced colorectal cancer was 4.7%(4/86),and all 4 mutations were codon 600 GTG>GAG(V600E).K-ras gene mutations were related to the location of advanced colorectal cancer,tumor differentiation,vascular tumor thrombus and nerve invasion,lymphatic metastasis,and liver metastasis(all P<0.05),but were not related to age,depth of invasion,or CEA level(all P>0.05).The BRAF gene mutation was related to the depth of invasion and the location of advanced colorectal cancer(both P<0.05),but was not associated with tumor differentiation,lymphatic metastasis,vascular tumor thrombus,nerve invasion,liver metastasis,age,or CEA level(all P>0.05).ConclusionsThe mutation rate of K-ras gene in the advanced colorectal cancer tissues is high,and point mutation is the main mutation,mainly the codon 12 mutation of exon 2.BRAF gene mutations in the cancer tissues of patients with advanced colorectal cancer are all V600E mutations.K-ras and BRAF gene mutations may play an important role in the occurrence and development of advanced colorectal cancer.