The detection of BRAF mutations and its clinical significance in colorectal cancer patients

Abstract

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.（Chin J Lab Med,2012,35:993-999） Key words: Colorectal neoplasms; Proto-oncogene proteins B-raf; Mutation