Xu Chen, Liu Ya-lan, Huang Jie, He De-ming, Hou Ying-yong, Ji Yuan, Hou Jun, Lu Shao-hua, Xu Jian-fang, Hu Qin, Shi Yuan, Zhao Li-jun, Tan Yun-shan
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhonghua Bing Li Xue Za Zhi. 2012 Oct;41(10):667-70. doi: 10.3760/cma.j.issn.0529-5807.2012.10.005.
To explore the clinical significance of KRAS mutation detection in colorectal adenocarcinoma.
Paraffin-embedded tissue specimens were obtained from 440 patients with colorectal adenocarcinoma. The genomic DNA was extracted. Mutations of exon 2 of KRAS gene were examined by PCR and direct sequencing.
Somatic mutations of KRAS gene were identified in 146 cases, with the mutation rate of 33.2% (146/440). Among these 146 patients, KRAS mutation involved codon 12 in 118 patients, including 35G > A (Gly12Asp, 62 cases), 35G > T (Gly12Val, 35 cases), 34G > T (Gly12Cys, 9 cases), 34G > A (Gly12Ser, 6 cases), 35G > C (Gly12Ala, 5 cases), and 34G > C (Gly12Arg, 1 case); in 27 patients the mutation involved codon 13, including 38G > A (Gly13Asp, 25 cases), 38G > C (Gly13 Val, 1 case) and 37G > T (Gly13 Cys, 1 case); and in one patient, the mutation involved codon 14 with 40G > A (Val14Ile). The status of KRAS or codon 12 mutations in colorectal adenocarcinoma was related to patients' gender (P = 0.021 and P = 0.030, respectively), and this significant correlation to females was conserved in clinical stage III (P = 0.007 and P = 0.003, respectively), but not in stages I, II, and IV. The status of KRAS or codon 12 mutations was also related to tumor stage. Between stage II and stage IV, the mutation rate of KRAS and codon 12 showed significant difference (P = 0.028 and 0.034, respectively). Between stage III and stage IV, only the codon 12 mutation rate showed significant difference (P = 0.011). Codon 13 mutation was not related to tumor stage.
About one third of patients with colorectal adenocarcinoma have KRAS gene mutation, which might be related to patients' gender; and could be consistently detected by PCR and direct sequencing.
探讨结直肠癌中KRAS基因突变检测的临床意义。
收集440例结直肠癌患者的石蜡包埋组织标本,提取基因组DNA,采用聚合酶链反应(PCR)及直接测序法检测KRAS基因第2外显子的突变情况。
146例患者检测到KRAS基因体细胞突变,突变率为33.2%(146/440)。其中,118例患者的KRAS基因突变发生在密码子12,包括35G>A(甘氨酸12天冬氨酸,62例)、35G>T(甘氨酸12缬氨酸,35例)、34G>T(甘氨酸12半胱氨酸,9例)、34G>A(甘氨酸12丝氨酸,6例)、35G>C(甘氨酸12丙氨酸,5例)、34G>C(甘氨酸12精氨酸,1例);27例患者的突变发生在密码子13,包括38G>A(甘氨酸13天冬氨酸,25例)、38G>C(甘氨酸13缬氨酸,1例)、37G>T(甘氨酸13半胱氨酸,1例);1例患者的突变发生在密码子14,为40G>A(缬氨酸14异亮氨酸)。结直肠癌患者KRAS基因或密码子12突变状态与患者性别有关(P值分别为0.021和0.030),且在临床Ⅲ期女性患者中这种显著相关性依然存在(P值分别为0.007和0.003),但在Ⅰ、Ⅱ、Ⅳ期患者中不存在。KRAS基因或密码子12突变状态也与肿瘤分期有关。Ⅱ期和Ⅳ期之间,KRAS基因及密码子12的突变率有显著差异(P值分别为0.028和0.034)。Ⅲ期和Ⅳ期之间,仅密码子12突变率有显著差异(P = 0.011)。密码子13突变与肿瘤分期无关。
约三分之一的结直肠癌患者存在KRAS基因突变,该突变可能与患者性别有关,且可通过PCR及直接测序法持续检测到。