Mutations of K-ras and v-raf murine sarcoma viral oncogene homolog B1 gene in colorectal cancer and their clinical significance

Abstract

Objective To investigate mutations of K- ras and v- raf murine sarcoma viral oncogene homolog B1(BRAF) genes in colorectal cancer and their clinical significance. Methods 412 cases of colorectal cancer tissue specimens were selected.Real- time quantitative polymerase chain reaction(Real- time PCR) was used to study the characteristics of K- ras and BRAF gene mutation sites and their relationship with clinicopathologic parameters. Results In 412 cases, the mutation rate of K- ras gene was 37.9%.The K- ras mutation rate in rectal cancer(45.2%) was higher than in colon cancer(28.8%, P< 0.05). The rate of single locus mutation was 35.4%, while the rate of double locus mutation was 2.2% and the rate of triple locus mutation was 0.2%.The K- ras mutation was most commonly located in codons 12 and 13,in which the rate of codon 12 was 32.0%.The mutation patterns of codon 12 included G12D(15.0%), G12V(9.5%), G12C(3.9%), G12S (2.9%), G12A(2.4%) and G12R(0.7%). The mutation pattern of thre codon 13 was G13D (6.1%).G→A was the most common mutation pattern.The K- ras gene mutation rate ofⅠ+Ⅱstage(30.4%) was lower than that ofⅢ+Ⅳstage(45.2%), with statistically significant difference(P< 0.05). Further analysis showed the mutation rate(5.9%)of G12V in TNM stageⅠ+Ⅱwas lower than that in stageⅢ+Ⅳ(13.0%, P< 0.05). The K- ras mutation was irrelevant to gender, age, tumor size, clinical tumor type, histological classification and lymphatic metastasis. The BRAFV600E mutation rate of colorectal cancer was 2.4%, and that of colon cancer(4.9%) was higher than rectal cancer(0.4%), with statistically significant difference(P<0.05). Conclusion In colorectal cancer, single locus mutation is most common in K- ras mutation, in which G12D was the main pattern. The mutation status of the G12V can probably promote the progresssion of colorectal cancer.The K- ras mutation rate in rectal cancer was higher than in colon cancer, while the BRAF mutation rate in colon cancer was higher than in rectal cancer.The mechanisms of K- ras and BRAF mutation in colon and rectal cancers may be different. Key words: K-ras gene; v-raf murine sarcoma viral oncogene homolog B1 gene; Gene mutation; Colorectal caner