摘要目的 检测中国结直肠癌患者中KRAS和BRAF基因突变率,分析KRAS和BRAF基因突变与患者临床病理特征的相关性.方法 收集2008年12月至2012年1月于北京大学肿瘤医院就诊的966例结直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、13位密码子以及BRAF基因外显子15的突变状态,分析基因突变与临床病理特征的相关性.结果 中国结直肠癌患者中KRAS与BRAF基因突变率分别为38.8％(375/966)与4.4％ (40/915),BRAF基因在KRAS野生型患者中的突变率为7.4％(40/540),且KRAS与BRAF基因突变为排他性.KRAS基因突变类型共有8种,以G12D、G12V 与 G13D最常见;BRAF基因突变类型共有3种,以V600E最常见.KRAS基因在女性、肿瘤分化程度较好及原发部位为右半结肠的患者中突变率明显升高(P值均＜0.05),且在≥65岁的患者中的突变率高于65岁以下患者(P=0.05);而BRAF基因在肿瘤分化程度较差及原发部位为右半结肠的患者中突变率较高(P值均＜0.05).KRAS和BRAF基因突变与肿瘤大小、浸润深度、淋巴结转移及TNM分期均无明显相关性(P值均＞0.05).结论 中国结直肠癌患者中,KRAS基因突变与性别、年龄、肿瘤分化程度及原发部位相关,而BRAF基因突变仅与肿瘤分化程度及原发部位有关;KRAS和BRAF基因突变与患者预后的相关性有待继续研究.

abstractsObjective To identify the mutation rate of KRAS and BRAF in Chinese patients with colorectal carcinoma (CRC),and to analyze the associations between KRAS/BRAF mutations and patients' clinicopatholgical characteristics.Methods Tumor specimens were obtained from 966 CRC patients treated in Peking University Caneer Hospital from December 2008 to January 2012.Mutation analysis of KRAS (codons 12 and 13 of exon 2) and BRAF (exon 15) was conducted by direct sequencing.The relationships between gene mutations and clinicopathological characteristics were statistically analyzed.Results The mutation rates of KRAS and BRAF in Chinese CRC patients were 38.8％ (375/966) and 4.4％ (40/915),respectively.Among patients with wild-type KRAS,the mutation rate of BRAF was 7.4％ (40/540).KRAS and BRAF mutations were mutually exclusive.Eight mutation types of KRAS were detected in this study with three common types G12D,G12V and G13D.Three mutation types of BRAF were detected with the most common type V600E.KRAS mutation rate was significantly higher in female,well-differentiated and right side colon tumors (all P ＜ 0.05).Also,the mutation rate in patients ≥ 65 years was higher tban that in patients ＜ 65 years (P =0.05).BRAF mutatiou rate was higher in poorly-differentiated and right side colon tumors (P ＜ 0.05).No significant associations were observed between KRAS/BRAF mutations and tumor size,depth of invasion,lymph node metastasis and TNM staging (P ＞ 0.05).Conclusions In Chinese CRC patients,KRAS mutations are associated with gender,age,tumor differentiation and primary tumor sites,while BRAF mutation is only associated with tumor differentiation and primary tumor sites.The correlations between KRAS/BRAF mutations and patients' prognosis need further investigation.