结直肠癌患者BRAF基因突变检测及其临床意义

摘要

Objective To determine the mutant status of BRAF gene in Chinese colorectal cancer (CRC) patients and analyze the association with clinicopathological parameters.Methods 676 CRC samples were collected in Cancer Institute/ Hospital,Chinese Academy of Medical Science from December 2009 to December 2011.The direct sequencing was conducted to detect mutations in the BRAF (exon 15 and exon 11).The correlation between mutant status with clinicopathological parameters were analyzed.Results Beside 10 colorectal cancer samples,among the 666 colorectal cancer patients 4.35％ (29/666) of the tumors harbored a BRAF mutation,of which 1.94％ (13/669) in exon 15 (V600E),2.39％ (16/670) in exon 11.Statistical analysis revealed that BRAF15 mutations appeared to occur more frequently in poor-differentiation tumors than high or moderate-differentiation tumors (5.81％ vs 1.46％,r =0.105,P=0.040).But BRAF15 mutations were not correlated with age,gender,smoking and drinking history,tumor site,tumor type,tumor(T/N) staging,histological type,or distant metastasis [r equals to 0.007,-0.018,-0.049,-0.023,-0.098,-0.038,0.040(0.034/0.059),0.065,0.042,respectively,P ＞ 0.05] ; BRAF11 mutations appeared to occur more frequently in patients with drinking history (6.02％vs 1.81％,r =0.093,P =0.035).However,age,gender,smoking history,tumor site,tumor type,tumor differentiation,tumor(N) staging,histological type,or distant metastasis showed no significant correlation with this mutation [r equals to-0.004,0.047,0.020,0.042,0.029,0.040,0.006 (-0.008),0.008,0.030,respectively,P ＞ 0.05].Conclusion A higher proportion of BRAF15 (V600E) mutations occurred in poor-differentiation tumors among the Chinese patients with CRC; BRAF11 mutations appeared more frequently in patients with drinking history.%目的 探讨中国结直肠癌患者鼠类肉瘤病毒癌基因同源物B1 (BRAF)基因突变与临床病理特征的关系及临床意义.方法 采用直接测序法检测2009年12月至2011年12月中国医学科学院肿瘤医院手术切除的676例结直肠癌患者组织标本中BRAF15及BRAF11外显子基因突变,并分析其与患者临床病理特征的关联性.结果 可有效检测的666例患者结直肠癌标本中的BRAF基因总突变率为4.35％ (29/666),其中BRAF15(V600E)突变率为1.94％ (13/669)；BRAF11突变率为2.39％ (16/670).结合临床病理特征分析,BRAF15突变与肿瘤分化程度相关(5.81％比1.46％),其分化程度越低,突变率越高(r=0.105,P=0.040).而突变率与患者年龄、性别、吸烟史、饮酒史、肿瘤原发部位、肿瘤形态、原发肿瘤分期(T分期/N分期)、肿瘤病理组织分型和是否有远处转移无相关性[r值分别为0.007、-0.018、-0.049、-0.023、-0.098、-0.038、0.040(0.034/0.059)、0.065、0.042,P均＞0.05].在有、无饮酒史患者中BRAF11突变频率差异有统计学意义(6.02％比1.81％,r=0.093,P=0.035).然而,其突变率与患者年龄、性别、吸烟史、肿瘤原发部位、肿瘤形态、肿瘤分化程度、原发肿瘤分期(N分期)、肿瘤病理组织分型和是否有远处转移无相关性[r值分别为-0.004、0.047、0.020、0.042、0.029、0.040、0.006(-0.008)、0.008、0.030,P均＞0.05].结论 我国结直肠癌患者BRAF15突变率随着肿瘤分化程度的降低逐渐升高；BRAF11在有饮酒史患者中突变率较高.