Cho J Y, Kim J H, Lee Y H, Chung K Y, Kim S K, Gong S J, You N C, Chung H C, Roh J K, Kim B S
Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Cancer. 1997 Feb 1;79(3):462-7. doi: 10.1002/(sici)1097-0142(19970201)79:3<462::aid-cncr6>3.0.co;2-k.
Mutations at codons 12, 13, and 61 of the three ras genes, H-ras, K-ras, and N-ras, convert these genes into active oncogenes. It appears that ras gene mutations can be found in a variety of tumor types. The purpose of this study was to evaluate the clinical significance of K-ras gene mutation in nonsmall cell lung carcinoma (NSCLC).
The authors analyzed 58 NSCLC patients for mutations at codons 12, 13, and 61 of the K-ras gene and correlated the findings with the tumor stage and patient survival. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and the direct nucleotide sequencing method were used to detect mutations after amplification of ras specific sequences by PCR.
Fourteen mutations (24%) of ras genes were found, all at codon 12 of the K-ras gene. GGT to GAT transition was the predominant mutational pattern. There was a significant association between K-ras mutation and the tumor stage (i.e., the higher the stage, the higher the mutation rate) (P = 0.014). Using univariate analysis, the presence of K-ras mutation in paraffin embedded tissue from patients who received treatment with curative intent was associated with a shorter survival (P = 0.039). The median survival duration for patients with or without K-ras mutation was 9 and 30 months, respectively. The Cox proportional hazards model also predicted a higher risk for patients with K-ras mutations (P = 0.047).
K-ras mutations, present in a subset of NSCLC, are associated with tumor progression and shortened patient survival.
H-ras、K-ras和N-ras这三种ras基因的第12、13和61密码子发生突变后，这些基因会转变为活性癌基因。ras基因突变似乎可见于多种肿瘤类型。本研究的目的是评估K-ras基因突变在非小细胞肺癌（NSCLC）中的临床意义。
作者分析了58例NSCLC患者K-ras基因第12、13和61密码子的突变情况，并将结果与肿瘤分期和患者生存率相关联。通过聚合酶链反应-单链构象多态性（PCR-SSCP）和直接核苷酸测序法，在经PCR扩增ras特异性序列后检测突变。
发现14个（24%）ras基因突变，均位于K-ras基因的第12密码子。GGT到GAT的转换是主要的突变模式。K-ras突变与肿瘤分期之间存在显著关联（即分期越高，突变率越高）（P = 0.014）。单因素分析显示，接受根治性治疗患者的石蜡包埋组织中存在K-ras突变与较短的生存期相关（P = 0.039）。有或无K-ras突变患者的中位生存期分别为9个月和30个月。Cox比例风险模型也预测K-ras突变患者的风险更高（P = 0.047）。
NSCLC患者亚组中存在的K-ras突变与肿瘤进展和患者生存期缩短相关。
