[Mutations of KRAS and BRAF in Chinese patients with colorectal carcinoma: analyses of 966 cases].

OBJECTIVE: 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' clinicopathological characteristics.

METHODS: Tumor specimens were obtained from 966 CRC patients treated in Peking University Cancer 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 than that in patients < 65 years (P = 0.05). BRAF mutation 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.