The Mutations Of K-ras And BRAF Gene In Colorectal Cancer And Its Clinical Significance

Objective: To investigate mutations of K-ras and BRAF gene in colorectal cancer andits clinical significance.Methods:412cases of colorectal cancer tissue specimens were selected. Real-timePCR was used to study the characteristics of K-ras and BRAF gene mutation sites andits relationship with clinicopathologic parameters.Results：In412cases, the mutation rate of K-ras gene was37.9%(156/412), in whichthe rate of single locus mutation was35.4%(146/412), while the rate of double locusmutation was2.2%(9/412) and the rate of triple locus mutation was0.2%(1/412).The K-ras mutation rate of rectal cancer (45.2%，103/228) was higher than coloncancer (28.8%,53/184)(P=0.001). The K-ras mutation was most common in codon12and13, in which the rate of codon12and codon13was respectively32.0%and6.1%.G>A was the most common mutation pattern. The mutation patterns of codon12included G12D (15.0%), G12V(9.5%), G12C(3.9%), G12S(2.9%), G12A(2.4%) andG12R(0.7%). The mutation pattern of codon13was G13D (6.1%). The K-ras mutationwas not correlated to gender, age, tumor size, clinical tumor type, histologicalclassification and lymphatic metastasis. The K-ras gene mutation rate of (I+II) stage(30.4%,62/204) was lower than the rate of (III+IV) stage (45.2%，94/208), withstatistically significant difference (P=0.002). Further analysis showed the mutationrate (5.9%，12/204) of G12V in TNM stage(I+II) was lower than the rate in stage(III+IV)(13%，27/208). That meaned, as the TNM stage increased, the Kras mutationrate rose(P=0.014). The BRAF mutation rate of colorectal cancer is2.4%(10/412), and the rate in colon cancer(4.9%) is higher than rectal cancer(0.4%),with statistically significant difference(P=0.001). In colorectal cancer, the K-ras genemutation was negatively correlated to BRAF gene mutation (P=0.016，r=－0.124). The BRAF gene mutation was closely correlated to pre-operation serum levels of CA199.The mutation rate of BRAF obviously increased as the serum CA199rose(P=0.04).According to different status of K-ras and BRAF gene in colorectal cancer, weclassified colorectal cancers to4types: Type I (wild type K-ras—wild type BRAF)accounted for59.5%(245/412); and type II (wild type K-ras—mutant type BRAF)accounted for2.4%(10/412); type III (mutant type K-ras—wild type BRAF) was38.1%(157/412); type IV (mutant type K-ras—mutant type BRAF) was0%(0/412). Further analysis showed that, the K-ras and BRAF mutation related coloncancers was mainly type II, and rectal cancer was mainly type III, and the differencehas statistical significance(P=0.001). The different gene status of K-ras and BRAF wasnot related to P53, Ki67, gender, age, clinical tumor type, histological classification,tumor size, pre-operation serum CEA or CA199(P＞0.05).Conclusions：In colorectal cancer, single locus mutation is most common in K-rasmutation, in which GGT> GAT (G12D) was the mainly pattern. The mutation status ofthe G12V can probably promote the progresssion of tumor cells. The K-ras mutationrate in rectal cancer was higher than colon cancer, while the BRAF mutation rate incolon cancer was higher than rectal cancer. The mechanisms of K-ras and BRAFmutation in colon and rectal cancers may be different. The classification according todifferent status of K-ras and BRAF gene may provide theoretical basis for choosingtarget in targeted therapy of colorectal cancer.